Gender difference in all-cause and cardiovascular mortality related to hyperglycaemia and newly-diagnosed diabetes

AIM/HYPOTHESIS: Diabetic women generally have a greater relative risk of cardiovascular diseases than diabetic men in comparison with non-diabetic women and men. Reasons for this excess risk in diabetic women is still unclear. The aim of this study is to evaluate whether the association between different degrees of hyperglycaemia and the risk of all-cause and cardiovascular mortality is different in women and men. METHODS: We analysed baseline glucose concentrations from 14 prospective European cohorts including 8172 men and 9407 women aged 30 to 89 years without history of diabetes, with a median follow-up of 8.3 years. Hazards ratios for all-cause and cardiovascular mortality were estimated adjusting for other risk factors. RESULTS: The mortality rates for all-cause and cardiovascular diseases were higher in men than in women in normoglycaemia, impaired glucose regulation and newly-diagnosed diabetes; the largest sex differential for cardiovascular mortality was in normoglycaemic people. The hazards ratios for all-cause and cardiovascular mortality were higher in newly-diagnosed diabetic women than men compared with normoglycaemic women and men, respectively; however, this sex difference was only significant for cardiovascular mortality. For smokers and for subjects with hypertension, hypercholesterolaemia or who where overweight, the hazards ratios for cardiovascular mortality in diabetic patients compared with normoglycaemic people were also higher in women than in men. CONCLUSIONS/INTERPRETATION: Newly diagnosed diabetic women showed higher relative risks for death from cardiovascular disease than diabetic men. Thus a more aggressive control of hyperglycaemia as well as of other cardiovascular risk factors might be appropriate in women with asymptomatic hyperglycaemia.     

Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention

Type 2 diabetes increases the risk of cardiovascular disease (CVD) two- to fourfold compared with the risk in non-diabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors (small, dense low-density lipoprotein [LDL] particles, low high-density lipoprotein [HDL] cholesterol, high triglycerides, elevated blood pressure, obesity, central obesity, hyperinsulinaemia, hyperglycaemia, etc.), the cause for an excess risk of CVD remains unknown. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol and blood pressure is similarly beneficial in diabetic and non-diabetic subjects. The treatment of hyperglycaemia reduces micro- and macrovascular complications in type 2 diabetic patients. Beta-blocking agents, angiotensin-converting enzyme inhibitors, aspirin, and thrombolytic therapy are also effective in the treatment of CVD amongst diabetic patients.     

Does NIDDM increase the risk for coronary heart disease similarly in both low- and high-risk populations?

Summary Finland has marked regional differences in the occurrence of coronary heart disease (CHD). Although the causes for these differences in CHD mortality and morbidity in the Finnish population are unknown, it offers an excellent opportunity to investigate the effects of non-insulin-dependent diabetes mellitus (NIDDM) on CHD risk in two populations differing significantly with respect to the occurrence of CHD. Therefore, we carried out a 7-year prospective population-based study including a large number of patients with NIDDM (East Finland: 253 men and 257 women; West Finland: 328 men, 221 women) and corresponding non-diabetic subjects (East Finland: 313 men, 336 women; West Finland: 325 men, 399 women). In both study populations the presence of NIDDM increased significantly the risk for CHD events (CHD mortality or all CHD events including CHD mortality or non-fatal myocardial infarction). Diabetic men had 3–4 fold higher and diabetic women 8–11-fold higher risk for CHD than corresponding non-diabetic subjects. Both non-diabetic and diabetic subjects had odds ratios (East vs West) for CHD events of about 2 indicating a similar East-West difference in the CHD risk. Regional difference was quite similar in men and women. These results imply that factors related to NIDDM, independently of conventional risk factors and the occurrence of atherothrombosis in the background population, must play a major role in the pathogenesis of atherosclerotic vascular disease in NIDDM diabetes.Abbreviations CHD Coronary heart disease - NIDDM non-insulin dependent diabetes mellitus - MI myocardial infarction     

CHD: a major burden in type 2 diabetes

Patients with type 2 diabetes have a two- to four-fold greater risk of cardiovascular mortality than non-diabetic individuals. In order to prevent coronary events in the diabetic population, it is important to treat modifiable cardiovascular risk factors. Data from the Multiple Risk Factor Intervention Trial (MRFIT) show that serum cholesterol level, systolic blood pressure level and cigarette smoking were significant predictors of cardiovascular disease mortality in men with and without diabetes. At every risk factor level, the absolute risk of age-adjusted coronary death rate was three times greater for diabetic men than non-diabetic men (p<0.0001). Patients with diabetes have an abnormal (dyslipidaemic) lipoprotein profile with high levels of very low density lipoprotein cholesterol and triglycerides, and a low level of high density lipoprotein cholesterol. Although levels of total cholesterol or low density lipoprotein (LDL) cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher levels of atherogenic small dense LDL particles. MRFIT data show that at any serum cholesterol level, diabetes confers two-three times the risk for a coronary event. These findings constitute the rationale for considering hypolipaemic therapy, e.g. with HMG-CoA reductase inhibitors (statins), in diabetic patients with dyslipidaemia, particularly in those with evidence of coronary heart disease. Evidence shows that statins significantly lower cholesterol, exhibit beneficial effects on many components of atherosclerosis, and can significantly reduce the incidence of stroke.     

Diabetes as a risk factor for stroke. A population perspective

Summary Stroke incidence, case fatality and mortality in diabetic patients were compared to non-diabetic subjects in a 35–74-year-old population in northern Sweden (target population 241,000). During an 8-year period, 1,544 stroke events in diabetic patients and 4,826 events in non-diabetic subjects were recorded. The crude incidence of stroke was 1,000 per 100,000 in the diabetic men vs 247 in the non-diabetic men (relative risk 4.1; 95% confidence interval 3.2–5.2). Among diabetic women, the crude incidence was 757 per 100,000 and 152 in non-diabetic women (relative risk 5.8; 95% confidence interval 3.7–6.9). The 28-day case fatality among men was similar in the diabetic and non-diabetic stroke patients (18.6 vs 17.1%; p=0.311), but significantly higher in diabetic women compared with non-diabetic women (22.2 vs 17.9%; p=0.02). When compared with the non-diabetic population, the overall mortality from stroke in the diabetic population (first and recurrent) was 4.4-times higher in male and 5.1-times higher in the female patients. Hypertension, atrial fibrillation, heart failure or myocardial infarction were all significantly more common in diabetic than in non-diabetic stroke patients. The population attributable risk, a crude estimate of all strokes ascribed to diabetes mellitus, was 18% in men and 22% in women. In Sweden, about 50 strokes are annually directly attributed to diabetes in a population of 100,000 in this age group.Abbreviations MONICA Multinational Monitoring of Trends and Determinants in Cardiovascular Disease - ICD International Classification of Diseases - CT computerised tomography - CI confidence interval - RR relative risk - CF case fatality     

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factorin

Summary Potential risk factors have been examined for association with mortality over a 10–12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 year in at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 18.6 in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes. Some other proven risk factors in non-diabetic populations had inconstant or absent associations in this group: other, as yet undefined, factors may be important in diabetes.     

Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study

Abstract. We investigated the age-, gender- and race-specific 1-year case fatality rates of diabetic and non-diabetic individuals with a myocardial infarction. Data were obtained from the Atherosclerosis Risk in Communities (ARIC) Surveillance Study, which monitors both hospitalized myocardial infarction and coronary heart disease (CHD) deaths in residents aged 35–74 years in four communities in the USA. The study population comprised 3242 hospitalized myocardial infarctions (HMIs) in diabetic subjects and 9826 HMIs in non-diabetic individuals between 1987 and 1997. Age-adjusted and gender- and race-specific odds ratios (OR) for 1-year case fatality comparing diabetic to non-diabetic patients were 2.0 (95% CI, 1.6–2.4) for white men and 1.4 (95% CI, 1.1–1.8) for white women. Further adjustment for severity of HMI, history of previous MI, stroke and hypertension, and therapy variables showed significantly higher case fatality in white diabetic men than in non-diabetic white men (OR=1.5; 95% CI, 1.2–1.9), but no significant association in the other race-gender groups. The age-adjusted odds of out of hospital death was significantly higher among white diabetic men (OR=1.7; 95% CI, 1.2–2.3), white women (OR=2.3; 95% CI, 1.4–3.8), and African-American women (OR=2.9; 95% CI, 1.5–5.9) as compared to their non-diabetic counterparts. In conclusion, diabetes is an independent factor for mortality within one year following a myocardial infarction among white men, and following out-of hospital coronary death in white men and women and in African-American women. It is possible that these differences could be explained, at least in part, by a less than optimal medical management of the high cardiovascular risk profile of these patients after hospital discharge.     

Lipoprotein lipase activity and serum lipoproteins in untreated Type 2 (insulin-independent) diabetes associated with obesity

Summary Serum lipoproteins and the heparin-releasable lipoprotein lipase (LPL) activity of adipose tissue and skeletal muscle were measured in 36 untreated obese patients with Type 2 (insulin-independent) diabetes and the values were compared with those of non-diabetic subjects of similar age, sex and relative body weight. In diabetic men, the LPL activity of adipose tissue was significantly reduced when expressed per tissue weight or per fat cell (p<0.01). Diabetic females had slightly but not significantly lower LPL activity in adipose tissue than the non-diabetic females. The muscle LPL activity was similar in diabetic and non-diabetic subjects of both sexes. When the diabetic men were classified according to fasting blood glucose, the patients with high glucose levels had lower adipose tissue LPL activity than those with moderate hyperglycaemia. In both diabetic and non-diabetic subjects, there was a significant positive correlation between HDL cholesterol concentrations and adipose tissue LPL activity. It is concluded that Type 2 diabetes influences adipose tissue LPL activity and plasma lipoprotein concentrations and that this effect is superimposed on the similar changes produced by obesity alone.     

Glycaemic control and obesity are the major determinants of diabetic dyslipidaemia in Hong Kong Chinese

OBJECTIVES: Dyslipidaemia plays a major role in the increased mortality in diabetes. Our aim was to address the quantitative abnormalities and determinants for lipid abnormalities in Chinese Type 2 diabetic patients. MATERIAL AND METHODS: In this study, we examined 1 279 Chinese type 2 diabetic patients and compared them with 959 non-diabetic control subjects. RESULTS: Of the 1 279 Type 2 diabetic patients, 588 (46.0%) were men and 691 (54.0%) were women. The mean age was 40.4 +/- 8.1 years (median: 41.0 years, range: 16-72 years). Compared to the 959 age- and sex-matched non-diabetic controls, diabetic patients were more obese, had higher blood pressure and adverse lipid profile characterized by high triglycerides and low high-density lipoprotein cholesterol. After adjusting for age, sex, smoking, obesity, use of lipid-lowering drugs and anti-diabetic agents, diabetic patients had higher risk of having hypertriglyceridaemia (>=2.3 mmol/L) and low high-density lipoprotein cholesterol (<0.9 mmol/L) than non-diabetic subjects. The corresponding odds ratios were 2.9 and 1.5, respectively. With multiple regression analysis (stepwise), dyslipidaemia was mainly associated with glycaemia, obesity and age in diabetic patients, and obesity, male gender and age in non-diabetic subjects. CONCLUSION: We have confirmed the high prevalence and increased risk of dyslipidaemia in Chinese type 2 diabetic patients. The long-term significance of these lipid abnormalities and their synergism on clinical outcomes requires further evaluation.     

Microalbuminuria predicts the development of serum lipoprotein abnormalities favouring atherogenesis in newly diagnosed type 2 (non-insulin-dependent) diabetic patients

Summary We studied the relationship of slight albuminuria (microalbuminuria) to serum lipid and lipoproteins in a representative group of middle-aged Type 2 (non-insulin-dependent) diabetic patients. A random sample of non-diabetic control subjects was also examined. Diabetic patients had both at diagnosis and after five years higher total, LDL- and VLDL-triglyceride levels and higher VLDL-cholesterol, but lower HDL-cholesterol levels than non-diabetic subjects. No consistent difference was found in LDL-cholesterol levels between diabetic and non-diabetic subjects. The prevalence of microalbuminuria (>35 mg/24 h) remained about the same in diabetic patients at both examinations (19–20%). The diabetic patients with persistent microalbuminuria were slightly hyperglycaemic and they tended to have lower creatinine clearance at the 5-year examination than those without persistent microalbuminuria. There were no differences in the blood pressure levels or the occurrence of hypertension between the diabetic groups with and without microalbuminuria. At the baseline examination, no differences were seen in serum lipids and lipoproteins between diabetic patients with and without microalbuminuria. In patients with persistent microalbuminuria. a statistically significant increase in VLDL-cholesterol (p<0.05) and VLDL- and LDL-triglyceride levels (p<0.05) and a decrease in HDL-cholesterol level (p<0.05) was seen at the 5-year follow-up. These changes could not be explained by age, sex, body mass index or HbA₁. In conclusion, persistent microalbuminuria predicts and aggravates abnormalities in lipoprotein composition and a decrease in HDL-cholesterol in patients with Type 2 diabetes mellitus. The excess cardiovascular morbidity and mortality in diabetic patients with increased albuminuria may, in part, be explained by these lipoprotein abnormalities.     

Non-insulin-dependent Diabetes and 11-Year Mortality in Asian Indian and Melanesian Fijians

This study reports 11-year all-cause and cause-specific mortality rates according to baseline glucose tolerance for a population-based sample of adult Melanesian and Indian Fijians (n = 2638), first surveyed in 1980. Risk factors for all-cause and cardiovascular disease (CVD) mortality in subjects with non-insulin-dependent diabetes (NIDDM) are also described. The baseline survey included 75 g oral glucose tolerance tests, measurements of blood pressure, body mass index, and triceps skinfold, assays of plasma cholesterol and triglycerides, electrocardiograms, and details of smoking habits and physical activity. Mortality status was ascertained for 2546 subjects through surveillance of death certificates, medical records and interview of subjects (or relatives). Mortality rates were increased in diabetic men and women of both ethnic groups: relative risks compared to subjects without diabetes at baseline were 1.7 (CI:0.9–3.1) and 2.0 (1.1–3.7) in Melanesian and 4.2 (2.7–6.5), 3.2 (1.9–5.7) in Indian men and women, respectively. A large proportion of mortality among diabetic subjects was attributed to CVD (62 %, 66 % in Melanesian and 54 %, 58 % in Indian men and women, respectively). Mortality rates tended to be higher in Melanesians than Indians, except for diabetic men where Indians had higher total and cardiovascular disease rates. In contrast to non-diabetic Fijians, diabetic women of both ethnic groups lost their relative protection from coronary heart disease (CHD). Cox regressions for diabetic subjects showed age and fasting plasma glucose to be independent predictors of all-cause mortality in men, and age, body mass index (inversely) and systolic blood pressure in women, but lipid concentrations, and cigarette smoking were not related. After accounting for conventional CVD risk factors, diabetes conferred significantly increased risk of total, CVD, and CHD mortality. The mortality experience of Melanesian and Indian Fijians with NIDDM is similar to that documented in developed populations, with excess mortality due to cardiovascular causes.     

The relationship of cardiovascular risk factors to the prevalence of coronary heart disease in newly diagnosed Type 2 (non-insulin-dependent) diabetes

Summary The relationship of cardiovascular risk factors to the prevalence of coronary heart disease was examined in 133 newly diagnosed Type 2 (non-insulin-dependent) diabetic patients (70 men, 63 women) aged from 45 to 64 years and in 144 randomly selected non-diabetic control subjects (62 men, 82 women) of the same age. The prevalence of coronary heart disease in diabetic patients, defined by symptoms and ischaemic ECG abnormalities in resting or exercise ECG, was more than threefold that in non-diabetic subjects. In multiple logistic analyses (including age, history of smoking, hypertension (+/-), serum cholesterol, HDL-cholesterol, triglycerides, 2-h post-glucose serum insulin, body mass index and diabetes (+/-)) carried out separately for men and women, diabetes showed an independent, significant association to coronary heart disease in both sexes. In addition, age and hypertension had a borderline association to coronary heart disease in men, whereas smoking and high 2-h postglucose serum insulin level showed a significant association in women.     

Relation of serum total sialic acid concentrations with diabetic complications and cardiovascular risk factors in Kuwaiti Type 2 diabetic patients

Serum total sialic acid is a marker of the acute phase response. Elevated levels have also been associated with cardiovascular disease in the general Caucasian population and especially in Type 2 diabetic subjects. The purpose of this study was to estimate serum total sialic acid concentrations among Kuwaiti Type 2 diabetic subjects and to investigate its association with macro and microvascular diabetes-related complications in that population. Serum total sialic acid levels were estimated by an enzymatic spectro-photometric assay in two groups of subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for their annual evaluation to the specialised diabetic clinic at the main university teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/-13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti diabetic women had significantly higher concentrations compared to diabetic men (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl) versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was unrelated to the degree of obesity. Significant correlations were found between serum total sialic acid concentrations and such cardiovascular risk factors as plasma levels of apolipoprotein B, low density lipoprotein cholesterol, triglycerides and uric acid in the diabetic subjects. Furthermore, there was a significant elevation in serum total sialic acid concentrations with increasing urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.     

Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease — putative association via common antecedents; further evidence from the whitehall study

Summary Fifteen year mortality rates are reported for men participating in the Whitehall Study in 1968–1970. Subjects were divided into four groups — normoglycaemic (centiles 1–95 of the blood glucose distribution: n=17,051), glucose intolerant (centiles 96–100: n = 999), newly diagnosed diabetic patients (n=56) and previously diagnosed diabetic patients (n=121) treated with diet±tablets. Relative risks for all causes mortality and from coronary and cardiovascular disease deaths were calculated. Age adjusted relative risks were highest in the newly diagnosed diabetic patients and were also increased in glucose intolerant and previously diagnosed diabetic men (p<0.05), but did not increase with increasing duration of diabetes. With adjustment for other risk factors, relative risks were similar in newly diagnosed and previously diagnosed diabetic men. There was no significant linear trend of adjusted relative risks with duration of diabetes when all diabetic men were pooled and person years at risk calculated. The lack of effect of duration upon relative risk together with other observations suggests common, possibly genetic, antecedents of both Type 2 (non-insulin-dependent) diabetes and coronary heart disease.     

Abnormalities in plasmas concentrations of lipoproteins and fibrinogen in Type 1 (insulin-dependent) diabetic patients with increased urinary albumin excretion

Summary Type 1 (insulin-dependent) diabetic patients with clinical nephropathy have a more than ten-fold increase in mortality of cardiovascular diseases compared with diabetic patients without nephropathy. The risk factors for cardiovascular disease, plasma concentrations of lipoproteins and fibrinogen, were investigated in 74 long-term diabetic patients: 37 with normal urinary albumin excretion, 20 with incipient nephropathy and 17 with overt clinical nephropathy based on urinary albumin excretion. The groups were matched according to sex, age and diabetes duration. The concentration of plasma cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride and fibrinogen rose with increasing urinary albumin excretion. The plasma concentrations of these lipoproteins and fibrinogen were 11–14% higher in the patients with incipient nephropathy and 26–87% higher in the patients with overt clinical ne phropathy compared with the patients without nephropathy. The plasma concentration of high density lipoprotein cholesterol was unaffected by albuminuria. Patients with normal urinary albumin excretion and HbA_1c>8.0% had significantly higher very low density lipoprotein- and lower high density lipoprotein cholesterol concentrations compared with patients with HbA_1c<8.0%. Simple addition of the described risk factors can only account for a minor part of the greatly increased cardiovascular mortality in patients with diabetic nephropathy. An additional and possibly more decisive factor might be a change in the arterial wall, a change which promotes lipid accumulation and/or facilitates thrombus formation.     

Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in Type II diabetes

Aims/hypothesis. Cardiovascular complications and particularly coronary heart disease are the main causes of morbidity and mortality in Type II (non-insulin-dependent) diabetes mellitus. Some studies have shown that hypertriglyceridaemia in diabetes is an independent cardiovascular risk factor. In the ECTIM study high apolipoprotein C3 and lipoprotein B:C3 concentrations (lipoparticles playing a role in triglyceride metabolism) were associated with myocardial infarction in non-diabetic subjects.¶Methods. We studied the relations between macroangiopathy and different cardiovascular risk factors and lipid variables in 188 Type II diabetic subjects.¶Results. Multivariate analysis showed that triglycerides, apo C3 and Lp B:C3, sex, duration of diabetes, microalbuminuria and age were independently associated with macroangiopathy. The study group was divided into quartiles according to apo C3 and Lp B:C3 concentrations: the prevalence of macroangiopathy and coronary heart disease were increased in upper quartiles.¶Conclusion/interpretation. Triglycerides apo C3 and Lp B:C3 were independent cardiovascular risk markers in our group of Type II diabetic patients. [Diabetologia (2000) 43: 703–708]     

Do women exhibit greater differences in established and novel risk factors between diabetes and non-diabetes than men? The British Regional Heart Study and British Women’s Heart Health Study

Aims/hypothesis  

Type 2 diabetes is associated with greater relative risk of CHD in women than in men, which is not fully explained by conventional cardiovascular risk factors. We assessed whether cardiovascular risk factors including more novel factors such as markers of insulin resistance, inflammation, activated coagulation and endothelial dysfunction differ more between diabetic and non-diabetic women than between diabetic and non-diabetic men, and the role of insulin resistance.     

5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects

The 5-year incidence of myocardial infarction and claudication was examined in a group of middle-aged patients (n = 133, 70 men and 63 women) with newly diagnosed non-insulin-dependent diabetes and nondiabetic control subjects (n = 144, 62 men and 82 women). The effects of general risk factors, plasma insulin level, and lipoprotein abnormalities on the incidence of myocardial infarction and claudication were also evaluated by univariate analyses in both diabetic patients and nondiabetic subjects and by multivariate analyses combining both groups. The age-adjusted incidence of myocardial infarction was higher both in diabetic men (19.4%) and diabetic women (11.0%) than in nondiabetic men (3.2%, p = 0.009) and nondiabetic women (3.0%, p = 0.047). Similarly, the age-adjusted incidence of claudication was higher among the diabetic patients (20.3% vs. 8.0% for men, p = 0.06; 21.8% vs. 4.2% for women, p = 0.003). None of the general risk factors (i.e., low density lipoprotein [LDL] cholesterol, blood pressure, smoking, and high density lipoprotein [HDL] cholesterol) showed an association with the risk of myocardial infarction either in the diabetic or nondiabetic groups of subjects, but an ischemic electrocardiographic abnormality at the baseline examination predicted myocardial infarction in diabetic men. In univariate analyses in diabetic subjects, high serum total cholesterol, low HDL cholesterol, high very low density lipoprotein (VLDL) cholesterol, and high total, LDL and VLDL triglycerides, and in nondiabetic subjects, high VLDL cholesterol and LDL triglycerides were associated with the appearance of claudication. In multivariate analyses including both diabetic and control subjects, only diabetes had an independent association with myocardial infarction, whereas smoking, high LDL triglycerides or VLDL cholesterol, and high fasting plasma insulin showed independent relations to claudication. The present results indicate that changes in lipoprotein composition characteristic of non-insulin-dependent diabetes are atherogenic and increase the risk of atherosclerotic vascular disease. Furthermore, high plasma insulin might also be involved in atherogenesis, independent of lipoprotein abnormalities.     

Lipids in type 2 diabetes

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.     

Early mortality from the time of diagnosis of Type 2 diabetes: a 5-year prospective cohort study with a local age- and sex-matched comparison cohort.

AIMS: To study patterns and predictors of early mortality in individuals with a new diagnosis of Type 2 diabetes, compared with a local age- and sex-matched comparison cohort. METHODS: A total of 736 individuals diagnosed with Type 2 diabetes between 1 May 1996 and 30 June 1998 and non-diabetic age- and sex-matched control subjects were studied. Follow-up was 5.25 years. Age- and gender-specific all-cause mortality odds ratios were calculated for the diabetic cohort compared with the non-diabetic comparator group. Mortality odds ratios were ascertained using conditional logistic regression. RESULTS: There were 147 deaths in the diabetic cohort [cardiovascular (42.2%), cancer (21.1%)]. Compared with the non-diabetic cohort, mortality odds more than doubled [odds ratio (OR) 2.47; 95% confidence interval (CI) 1.74, 3.49]. These increased odds were present in all age bands (including those aged > 75 years at diagnosis) for both cardiovascular and non-cardiovascular causes. In women, a new diagnosis of Type 2 diabetes was associated with a sevenfold increase in mortality odds in those aged 60-74 years (OR 7.00; 95% CI 2.09, 23.47). CONCLUSIONS: Type 2 diabetes is associated with a 2.5-fold increase in the odds of mortality in both men and women over the first 5 years from diagnosis. Our data strongly support the contention that the mortality risk associated with Type 2 diabetes essentially exists from, or may even predate, the time of diagnosis.