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.     

Congenital anomalies and first life year surveillance in Type 1 diabetic births

Aims To evaluate the rate of congenital anomalies (CA) and the reasons for mortality from 22 weeks of gestation until 1 year of age in births by Type 1 diabetic mothers. Methods Population‐based cohort study using combined data from four national health registers in Finland during 1991–1995, including 954 singleton pregnancies complicated by Type 1 diabetes. Results Sixty births (629/10 000) involved registered major CA, of which 68% (n = 41) were isolated and 22% (n = 13) multiple anomalies, and in six cases, a syndrome was diagnosed (10%). After the exclusion of syndromes, the total number of anomalies was 73. Of the malformed infants, 63% were boys. The total rate of deaths among births until 1 year of age was higher in diabetic than in non‐diabetic mothers (19.9/1000 vs. 8.1/1000): especially the rates of stillborns (odds ratio 2.4; 95% confidence interval 1.2–4.7) and post‐neonatal deaths (3.8; 1.6–9.2) were higher. Of perinatal mortality (PNM) from the 22nd gestational week to the age of 7 days (13.6/1000), 23% were due to CA, 23% to prematurity, and the rest were intrauterine, mostly unexplained, deaths. Respiratory distress syndrome was the main cause of death among infants. Conclusions The rate of CAs in Type 1 diabetic pregnancies is still high, but their proportion as a cause of PNM has decreased. Though PNM rate was low, post‐neonatal mortality was significantly increased, reflecting the shift of deaths from the perinatal period to a later age.     

Cardiovascular Morbidity and Mortality in Type 2 Diabetic Patients: a 22-year Historical Cohort Study in Dutch General Practice

A historical cohort study was performed to assess cardiovascular morbidity and mortality in Type 2 (non-insulin-dependent) diabetic patients. The data were collected from 1967 to 1989 in four Dutch general practices performing the Continuous Morbidity Registration Nijmegen. Each newly diagnosed Type 2 diabetic patient fulfilling the WHO criteria (n = 265) was matched to a control patient for practice, sex, age, and social class. Inclusion started in 1967, the first year of the still ongoing, Continuous Morbidity Registration Nijmegen. On average, a follow-up of 6.8 years (range 1 month—22 years) was realized. Compared to the non-diabetic control patients, the Type 2 diabetic patients showed higher cardiovascular morbidity (risk ratio 1.76, 95 % CI 1.34–2.30) and a higher mortality rate (risk ratio 1.54, 95 % CI 1.07–2.23). Mortality after 10 years was 36 % vs 20 % (p < 0.01), the median survival time 16 years vs 19 years. The cumulative survival rates were significantly different (p < 0.01) between patients and controls in the age group 65–74 years. The higher mortality in Type 2 diabetic patients was completely due to an excess of cardiovascular death (risk ratio 2.05, 95 % CI 1.24–3.37).     

Current status of Type 2 (non-insulin-dependent) diabetic subjects on dialysis therapy in Japan

Summary According to a national survey of dialysis patients in Japan conducted by the Japanese Society for Dialysis Therapy, there were 1,033 patients on dialysis in the Shiga area which has a population of about 1.2 million. Of these 1,033 dialysis patients 140 were the result of diabetic nephropathy. From four hospitals affiliated to Shiga University of Medical Science the medical records of 90 diabetic subjects on dialysis therapy were reviewed and various clinical parameters were analysed and compared with those of patients with chronic glomerulonephritis. Since only one patient had Type 1 (insulin-dependent) diabetes, the remaining 89 with Type 2 (non-insulin-dependent) diabetes were used for this study. The significantly different variables between patients with Type 2 diabetes and chronic glomerulonephritis were age (60.4 vs 54.6 years,p<0.05), BMI (22.4 vs 20.6 kg/m²,p<0.001), cardiothoracic ratio (56.4 vs 53.3%,p<0.001), mean blood pressure (110 vs 117 mm Hg,p<0.05), serum creatinine (9.0 vs 11.5 mg/dl,p<0.001), serum urea-N (98.2 vs 115.5 mg/dl,p<0.001), serum total protein (6.0 vs 6.5 g/dl,p<0.001) and serum albumin (3.5 vs. 3.9 g/dl,p<0.001). Serum levels of cholesterol and triglyceride were not significantly different between two groups, though the prevalence of electrocardiogram abnormalities, oedema, neuropathy, myocardial infarction and cerebrovascular diseases was significantly higher in the Type 2 diabetic group. These results suggested that Type 2 diabetic patients with end-stage renal disease were older, more malnurished, fluid overloaded and multi-morbid as a result of vasculopathy and neuropathy. However, the analysis of causes of death in Type 2 diabetic patients (n=24) and patients with chronic glomerulonephritis (n=26) failed to provide evidence of higher risk of cardiac death in the Type 2 diabetic group compared to the group with chronic glomerulonephritis (37.5 vs 34.6%, NS). In the Type 2 diabetic patients on dialysis therapy, malnutrition, fluid overload and neuropathy appeared to be significant factors influencing the outcome of the therapy, while in patients with chronic glomerulonephritis, age and vascular morbidities were considered to be major risk factors for the prognosis.     

Prognosis after stroke in diabetic patients. A controlled prospective study

Summary Cohorts of diabetic (n=121) and non-diabetic (n=584) patients were prospectively followed for up to ten years after having suffered from a stroke. All but six of the diabetic patients had Type 2 (non-insulin-dependent) diabetes mellitus. The diabetic patients had more risk factors associated with stroke: heart failure (p<0.001) and angina pectoris (p<0.001), than the non-diabetic patients. Neither body mass index nor blood pressure levels differed between the groups at admission. Haematocrit levels were higher in the diabetic group (p<0.01). The diabetic patients were more commonly afflicted by cerebral embolism and to a lesser extent by transient ischaemic attacks than the nondiabetic patients. When calculated by log-rank tests, the diabetic group had an increased risk of death (p<0.001), recurrent stroke (p=0.001), and of myocardial infarction (p=0.001) after the initial stroke. Autopsy-verified causes of death between the groups did not differ significantly, although half of all deaths during the period one to six months after stroke were caused by pulmonary embolism in the diabetic group. Thus, diabetes increases the risk of death after a stroke, and it also increases among stroke survivors the risk of recurrent stroke and myocardial infarction.     

Plasma N-terminal pro-B-type natriuretic peptide and mortality in type 2 diabetes

Aims/hypothesis Raised N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with a poor cardiac outcome in non-diabetic populations. Elevated NT-proBNP predicts excess morbidity and mortality in diabetic patients with an elevated urinary albumin excretion rate. This study investigated the prognostic value of NT-proBNP in a cohort of type 2 diabetic patients. Subjects, materials and methods In a prospective observational follow-up study, 315 type 2 diabetic patients with normoalbuminuria (n=188), microalbuminuria (n=80) and macroalbuminuria (n=47) at baseline were followed for a median (range) of 15.5 (0.2–17.0) years. Plasma NT-proBNP concentrations were determined by immunoassay at baseline. Endpoints were overall and cardiovascular mortality. Results Of the patients, 162 died (51%), 119 of them (74%) due to cardiovascular causes. All-cause mortality was increased in patients with NT-proBNP in the second and third tertiles (hazard ratios [95% CI] compared with the first tertile, 1.70 [1.08–2.67] and 5.19 [3.43–7.88], p<0.001). These associations persisted after adjustment for urinary albumin excretion rate, glomerular filtration rate and conventional cardiovascular risk factors (covariate adjusted hazard ratios 1.46 [0.91–2.33] and 2.54 [1.56–4.14], p<0.001). This increased mortality was attributable to more cardiovascular deaths in the second and third NT-proBNP tertile (unadjusted hazard ratios 1.63 [0.96–2.77] and 4.88 [3.01–7.91], p<0.001; covariate adjusted 1.37 [0.79–2.37] and 2.26 [1.27–4.02], p=0.01). When patients with normo-, micro- and macroalbuminuria were analysed separately, NT-proBNP levels above the median (62 ng/l) were consistently associated with increased overall and cardiovascular mortality in all three groups (p<0.001). Conclusions/interpretation In patients with type 2 diabetes, elevated circulating NT-proBNP is a strong predictor of the excess overall and cardiovascular mortality, this predictor status being independent of urinary albumin excretion rate and conventional cardiovascular risk factors.     

Social deprivation and mortality in adults with diabetes mellitus

To investigate the relationship between measures of social deprivation and mortality in adults with diabetes, data from 2104 randomly selected adults (>16 years of age) with Type 1 and Type 2 diabetes mellitus from 8 hospital out-patient departments were analysed. A total of 38 % of subjects had Type 1 (diagnosed before the age of 36 years and treated with insulin), 55 % were male and 85 % Caucasian. During a follow-up period (mean (SD) of 8.4 (0.9) years), 293 (14 %) of the subjects died, the most commonly recorded cause of death being cardiovascular disease. Duration adjusted odds ratios (OR) and 95 % confidence intervals (CI) were calculated separately for Type 1 and Type 2 subjects. The mortality rates for men were higher than for women (Type 1: OR 1.27, CI 0.61–2.62; Type 2: OR 1.79, CI 1.27–2.52); were higher for those of lower vs higher social class (Type 1: OR 1.34, CI 0.61–2.96; Type 2: OR 2.0, CI 1.41–2.85); and were higher for those who left school before 16 years of age compared to those who left school at or after 16 years of age (Type 1: OR 3.98, CI 1.96–8.06; Type 2: OR 2.86, CI 1.93–4.25). Subjects who were unemployed had a higher mortality rate than those employed at the time of the study (Type 1: OR 3.10, CI 1.67–5.79; Type 2: OR 2.88, CI 2.12–3.91) and those living in council housing had a greater mortality than those who were living in other types of housing (Type 1: OR 2.57, CI 1.35–4.91, Type 2: OR 2.76, CI 2.05–3.73). Also for both Type 1 and Type 2 subjects mortality was significantly higher in those subjects who had a least one diabetic complication at baseline and reported one or more hospital admissions in the previous year and in Type 2 subjects with poor glycaemic control. After adjusting for duration of diabetes, hospital admissions, and the presence of diabetic complications, being unemployed, male, in poor glycaemic control (Type 2 only), and less educated were significant risk factors for mortality (p<0.001). These results suggest that there are important indicators of social deprivation which predict mortality over and above diabetic health status itself. Locally targeted action will be required if these inequalities in health experienced by people with diabetes are to be reduced. © 1998 John Wiley & Sons, Ltd.     

Factors associated with basal metabolic rate in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary To examine determinants of basal metabolic rate we studied 66 Type 2 (non-insulin-dependent) diabetic and 24 healthy age- and weight-matched control subjects with indirect calorimetry and infusion of [³H-3-] glucose. Eight Type 2 diabetic patients were re-studied after a period of insulin therapy. Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 ± 1.9 J · kg LBM^–1-min^–1 vs 90.7 ± 2.8 J · kg LBM^–1;min^–1; p<0.01) and decreased significantly with insulin therapy (p <0.01). The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 ± 29.9 vs 789.3 ± 41.7 mol/min; p <0.001) and decreased after insulin therapy (p <0.01). Hepatic glucose production correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.49; p <0.001) and in control subjects (r = 0.50; p<0.05). Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 ± 0.05 vs 1.37 ± 0.08 mol · kg LBM^–1 · min^–1'; p <0.01) and decreased significantly after insulin therapy (p <0.05). The rate of lipid oxidation correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.36; p <0.01) and in control subjects (r = 0.51; p <0.01). These data demonstrate that basal metabolic rate, rates of hepatic glucose production and lipid oxidation are interrelated in Type 2 diabetic patients. A reduction of the hepatic glucose production, however, is associated with a reduction in lipid oxidation, which in turn, may result in a reduction in basal metabolic rate.     

Elevated serum uric acid — a facet of hyperinsulinaemia

Summary In a representative sample of the adult Jewish population in Israel (n=1016) excluding known diabetic patients and individuals on antihypertensive medications, serum uric acid showed a positive association with plasma insulin response (sum of 1- and 2-hour post glucose load levels) in both males (r=0.316, p<0.001) and females (r=0.236, p<0.001). This association remained statistically significant in both sexes (p<0.001) after accounting by multiple regression analysis for age and major correlates of serum uric acid, i.e. body mass index, glucose response (sum of 1- and 2-hour post load levels), systolic blood pressure and total plasma triglycerides. The net portion of the variance of serum uric acid attributable to insulin response was 12% in males and 8% in females, the total variance accountable by all these variables being 17% and 19% respectively. We conclude that elevated serum uric acid is a feature of hyperinsulinaemia/insulin resistance.     

Plasma apolipoprotein (a) is increased in Type 2 (non-insulin-dependent) diabetic patients with microalbuminuria

Summary Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/1, 95 % confidence interval 117–324) and albuminuria (n = 19, 281 U/1,165–479) were higher than in non-diabetic control subjects (n = 140,107 U/1, 85–134,p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/1, 76–169,p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40,193 U/1,126–298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/1, 143–306 vsn = 54, 116 U/1, 78–173,p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.     

Orosomucoid in urine predicts cardiovascular and over-all mortality in patients with Type II diabetes

Aims/hypothesis: Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes. Methods: In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. Results: We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00–6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31–73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA_{1 c}, plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. Conclusion/interpretation: We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors. [Diabetologia (2002) 45: 115–120] Received: 24 July 2001 and in revised form: 17 September 2001     

Determinants of carotid artery wall thickening in young patients with Type 1 diabetes mellitus

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age ≤ 40 years, mean 27.9 ± 6.5) with a diabetes duration ≥ 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 ± 0.06 mm in control group 1 and 0.50 ± 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: −0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 ± 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 ± 0.17 vs 0.55 ± 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of ≤ 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients. © 1998 John Wiley & Sons, Ltd.     

Genetic influence of the R/Q353 genotype on factor VII activity is overwhelmed by environmental factors in Chinese patients with Type II (non-insulin-dependent) diabetes mellitus

Summary We studied the effects of genetic and environmental influences on factor VII coagulant activity (VIIc) in Chinese diabetic patients (263 with Type II [non-insulin-dependent] diabetes mellitus, 78 with Type I [insulin-dependent] diabetes mellitus) and 143 normal control subjects. VIIc was measured by a one-stage biological assay. The R/Q353 or Msp1 polymorphism at codon 353 of the factor VII gene was detected after Msp1 digestion of polymerase chain reaction-amplified genomic DNA. In both diabetic and control subjects the allele frequencies of the R (M1) and Q (M2) alleles were 0.96 and 0.04; the corresponding reported frequencies in Caucasians being 0.90 and 0.10: VIIc were 21 % lower in Chinese control subjects and Type I diabetic patients with R/Q, compared with R/R subjects (p < 0.001 and p < 0.05). The corresponding difference was 4 % for Type II diabetc patients (p = NS). Type II diabetic patients had higher mean VIIc levels than control subjects and Type I diabetic patients (p < 0.01); they were also older, and had higher serum creatinine and triglyceride (all p < 0.01). They also had higher VIIc levels than an age-matched older control group (p < 0.01; n = 182) in whom the genotype effect was clearly seen. On stepwise linear regression analysis, the significant independent determinants of VIIc were serum triglyceride (contributing 20 % and 25 % to variance in control subjects and diabetic patients), the R/Q353 genotype (contributing to 12 % of the variance in control subjects but only 1 % in diabetic patients), age and total cholesterol in all subjects, and in the diabetic patients female sex, urinary albumin excretion rate and serum creatinine. VIIc was higher in diabetic patients with macroangiopathy and retinopathy (both p < 0.0001). We conclude that compared with Caucasians, the Q allele frequency is significantly lower in these Chinese subjects. Plasma VIIc is determined by both genetic and environmental influences such that in Chinese Type II diabetic patients, the effect of environmental factors predominates, almost negating the influence of the R/Q353 genotype. High VIIc may contribute to the increased cardiovascular risk in Type II diabetic patients. [Diabetologia (1998) 41: 760–766] Received: 24 October 1997 and in final revised form: 28 January 1998     

Five-year mortality in elderly French subjects from the PAQUID epidemiological survey: the burden of diabetes

We describe the 5-year mortality and its risk factors in a cohort of elderly people with and without known diabetes mellitus. The PAQUID cohort was representative of the population older than 65 living in Gironde, south-west France. Potential mortality risk factors were collected during a baseline evaluation, using a health questionnaire, from 68.9 % of a randomly selected sample of over-65s in 1988. A total of 237 subjects (8.5 %) had diabetes. Annual review occurred for 5 years and cause of any death was ascertained from family doctors. After 5 years, 623 people (22.3 %) had died, of whom 576 were non-demented; 30.0 % of the diabetic group versus 20.3 % of the non-diabetic group had died. Survival of the known diabetic group was lower than that of the non-diabetic group (p < 0.001), although this excess mortality was significant only in the 65 to 75 age range (relative risk 1.8; 95 % confidence interval 1.2 to 2.8, p = 0.04). Cardiovascular mortality rate did not differ between the diabetic and non-diabetic groups (RR 1.2 [0.8–2.0]). Death related to neoplasia was significantly higher in the known diabetic group (RR 2.2 [1.2–3.3], p = 0.01). In the final model, integrating diabetes as a mortality risk factor in the total cohort, known diabetes at the baseline examination was an independent risk factor for mortality (RR 1.4 [1.0–1.8], p = 0.01), in addition to tobacco use, hypertension and functional dependency. These results confirm suggestions that diabetes increases mortality in the over-65 age group, perhaps with an adverse interaction with other pathology. © 1998 John Wiley & Sons, Ltd.     

Variation of Diabetes Mellitus Prevalence in General Practice and Its Relation to Deprivation

This is an observational study to compare age standardized diabetes prevalences and relate these to socio-economic measures of deprivation. It includes data from eight general (family) practices in the Bristol, UK, area with no ethnic minorities affecting diabetes prevalence. A total population of 71 599 was covered, including 181 Type 1 and 901 Type 2 diabetic patients, 91 of whom were controlled with insulin, 499 with oral hypoglycaemics, and 311 with diet alone. Actual Type 1 and Type 2 diabetes prevalences were standardized to what they would be if each practice had the UK national age profile. Total standardized diabetes prevalence varied from 1.31 % to 2.51 % (p < 0.001) and Type 2 diabetes prevalence from 0.97 % to 2.29 % (p < 0.001). There was no significant variation in the prevalence of Type 1 diabetes. The Spearman rank correlation coefficient indicated a significant association between standardized diabetes prevalence and two measures, the Jarman and Townsend indices, of deprivation in the electoral ward where each practice was situated. Total standardized diabetes prevalence was significantly correlated with each of the Jarman and Townsend indices (r_s = 0.76, p < 0.05). Standardized Type 2 diabetes prevalence was similarly significantly correlated to each deprivation index (r_s = 0.74, p < 0.05). Type 2 diabetes prevalence is affected by socio-economic factors with implications for health targets and capitation based budgets.     

Relationship Between Blood Pressure and Urinary Albumin Excretion Rate in Young Danish Type 1 Diabetic Patients: Comparison to Non-diabetic Children

In 1989 a nation-wide investigation of blood pressure and urinary albumin excretion rate (AER) was carried out in 506 boys and 441 girls with Type 1 diabetes (approximately 80 % of total) treated at 22 paediatric departments. In addition a reference population from 1979 consisting of 663 healthy non-diabetic children (334 boys, 329 girls) served as a control group with respect to blood pressure and body mass index. Microalbuminuria was defined as AER of 20–150 μg min^-1 in at least two out of three timed overnight urine collections and was diagnosed in 30 adolescents (16 boys, 14 girls). Five patients (3 boys, 2 girls) had overt proteinuria (AER: > 150μg min^-1). Age-related percentile charts based on one blood pressure reading were provided for normoalbuminuric diabetic patients and the healthy control group. The study revealed an increase in arterial blood pressure during the period of the pubertal growth spurt for the diabetic and non-diabetic group. The changes were most pronounced for systolic blood pressure. No statistically significant difference was observed in systolic and diastolic blood pressure between normoalbuminuric diabetic children and healthy control children. However, diabetic females aged 15–18 years had significantly higher diastolic blood pressure (75 ± 1 mmHg, n = 139, mean ± SE) than healthy control females (72± 1 mmHg, n = 155, p ± 0.01), and significantly (p ± 0.001) higher body mass index (diabetic females: 22.3± 0.2 kg m^-2 vs healthy females: 20.9± 0.2 kg m^-2, mean± SE). Boys aged from 15 to 18 years with Type 1 diabetes had significantly higher systolic blood pressure (123± 1 mmHg, n = 164) than girls (117± 1 mmHg, n = 139, p± 0.0001), while girls aged from 15 to 18 years had significantly higher diastolic blood pressure (75± 1 mmHg, n = 139) than boys (72± 1 mmHg, n = 72, p ± 0.01). Among the 30 adolescents with persistent microalbuminuria, 18 (10 boys, 8 girls) had diastolic blood pressure above the upper quartile for normoalbuminuric patients, while 2 out of 5 with macroalbuminuria had diastolic blood pressure above this limit. By multiple logistic regression the only risk determinants for elevated urinary albumin levels were age and diastolic blood pressure. These findings suggest that elevated arterial blood pressure is related to the increased prevalance of microalbuminuria observed in adolescents with Type 1 diabetes.     

Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in Type 2 (non-insulin-dependent) diabetic and non-diabetic subjects

Summary The purpose of the present study was to examine 10-year cardiovascular morbidity and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus and non-diabetic control subjects and to evaluate the effects of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia in diabetic patients on cardiovascular mortality. Furthermore, the extent to which the above-mentioned factors could contribute to the excessive cardiovascular mortality observed in diabetic patients was examined. In the years 1979–1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2 diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45–64 years were studied. Both groups were re-examined in the years 1985–1986 and 1991–1992. The impact of different factors on cardiovascular mortality was examined by univariate analyses after adjustment for age and sex and by multiple logistic regression analyses. The age-standardized total and cardiovascular mortality rates were substantially higher in diabetic men (17.8 and 15.0%, total and cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and 16.6%, p<0.01 for both) than in non-diabetic control men (5.2 % both total and cardiovascular mortality) and women (4.2 and 2.2 %). Cardiovascular mortality was not related to the treatment modality (diet, oral drugs, insulin) at 5 years from diagnosis. Use of diuretics, beta-blocking agents or their combination at baseline did not make a significant contribution to cardiovascular mortality either. In multiple logistic regression analysis on diabetic patients, age, LDL triglycerides, smoking, blood glucose and ischaemic ECG at baseline had independent associations with cardiovascular mortality. Interestingly, urinary albumin excretion rate measured at 5-year examination also predicted 10-year cardiovascular mortality after adjustment for the effects of major risk factors including lipoprotein abnormalities, but its predictive power reduced to a nonsignificant level when the effect of plasma glucose was taken into account. The relative risk of cardiovascular mortality associated with diabetes was 8.2 after allowing for age alone, but it declined to 3.7 when all contributing factors from the baseline examination (except blood glucose) were taken into account. In conclusion, the present results indicate that LDL triglycerides and/or other changes in lipoprotein composition characteristic of Type 2 diabetes and manifesting as elevated serum triglycerides are atherogenic and they strongly predict increased cardiovascular mortality. Furthermore, it is hypothesized that the consequences of long-term hyperglycaemia could explain a large proportion of the remaining excessive cardiovascular mortality risk among Type 2 diabetic patients.     

Impact of initial treatment on renal function in newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus

Summary The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p<0.01); fasting plasma glucose (p<0.001); glycated haemoglobin (HbA₁) (p<0.001); systolic blood pressure (p<0.01); and diastolic blood pressure (p<0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min^–1 (p<0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min^–1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) g·min^–1 (p<0.01). Changes in glomerular filtration rate ( values) were inversely correlated with presentation values (p<0.001), and positive relationships were observed with effective renal plasma flow (p<0.01), and glycated haemoglobin (p<0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min^–1 demonstrated significant reduction in glomerular filtration rate (n=31; p<0.001), whilst those with original values less than 120 ml·min^–1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p<0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p<0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min^–1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.     

Effects of alcohol consumption on mortality in patients with Type 2 diabetes mellitus

Aims/hypothesis Moderate alcohol intake has been associated with increased life expectancy due to reduced mortality from cardiovascular disease. We prospectively examined the effects of alcohol consumption on mortality in Type 2 diabetic patients in Switzerland.Methods A total of 287 patients with Type 2 diabetes mellitus (125 women, 162 men), recruited in Switzerland for the WHO Multinational Study of Vascular Disease in Diabetes, were included in this study. After a follow-up period of 12.6±0.6 years (means ± SD), mortality from CHD and from all causes was assessed.Results During the follow-up, 70 deaths occurred (21 from CHD, 49 from other causes). Compared with non-drinkers, alcohol consumers who drank alcohol 1 to 15 g, 16 to 30 g and 30 g or more per day had the following risk rates of death from CHD: 0.87 (95% CI: 0.25 to 2.51, NS), 0.00 (95% CI: 0.00 to 0.92, p less than 0.05) and 0.37 (95% CI, 0.01 to 2.42, NS), respectively. The corresponding risk rates of death from all causes were 1.27 (95% CI: 0.68 to 2.28, NS), 0.36 (95% CI: 0.09 to 0.99, p less than 0.05) and 1.66 (95% CI: 0.76 to 3.33, NS).Conclusions/interpretation In Swiss Type 2 diabetic patients moderate alcohol consumption of 16 to 30 g per day was associated with reduced mortality from CHD and from all causes. Alcohol intake above 30 g per day was associated with a tendency towards increased all-cause mortality.Abbreviations HR Hazard ratio - ICD-9 International Classification of Disease 9 - RR risk rate     

Prevalence of hypertension in Type 1 (insulin-dependent) diabetes mellitus

Summary The prevalence of hypertension in a representative sample (n=10202) of the Danish general population aged 16–59 years was assessed to 4.4% based on three blood pressure readings. In Type 1 (insulin-dependent) diabetic patients of similar age (n=1703) the prevalence was determined in a similar way to 14.7% (p<0.00001). The excess prevalence in Type 1 diabetic patients was due to hypertension in patients with incipient and clinical nephropathy as the prevalence of hypertension among diabetic patients with normal urinary albumin excretion (essential hypertension) was 3.9%, similar to that observed in the general population. The patients with Type 1 diabetes and essential hypertension had higher systolic (146±19 vs 133±18 mmHg, p<0.00001) and diastolic blood pressure (87±12 vs 79±7mmHg, p<0.00001), but less changes in the eye background than patients with incipient nephropathy (urinary albumin excretion 30–300 mg/24 h) (p<0.03), indicating that the two groups were also different with respect to other microangiopathic lesions. Patients with essential hypertension were defined as having a normal urinary albumin excretion before and during antihypertensive treatment (if any). They were followed-up for a 58 (6–234) month period. We confirmed that hypertension is more common among Type 1 diabetic patients than in the general population and found the prevalence of essential hypertension similar in Type 1 diabetic patients to the non-diabetic population. This supports our hypothesis that hypertension is very unlikely to be the cause of diabetic nephropathy.