Mortality and causes of death in a national sample of diabetic patients in Taiwan

OBJECTIVE: To determine the mortality rate, causes of death, and standardized mortality ratio (SMR) in Taiwanese diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 256036 diabetic patients (118855 men and 137181 women, aged 61.2 +/- 15.2 years) using the National Health Insurance were assembled during the years 1995-1998 and followed up to the end of 2001. Deaths were verified by indexing to the National Register of Deaths. Underlying causes of death were determined from death certificates coded according to the ninth revision of the International Classification of Diseases. The general population of Taiwan was used as reference for SMR calculation. RESULTS: With a total of 1124348.4 person-years of follow-up, 43888 patients died and the crude mortality rate was 39.0/1000 person-years. Mortality rates increased with age, and diabetic men had a significantly higher risk of death than women. However, mortality rate ratio for men versus women attenuated with increasing age. The overall SMR was 1.63 (1.62-1.65), and SMRs also attenuated in the elderly. Causes of death ascribed to diabetes; cancer; cardiopulmonary disease; stroke; disease of arteries, arterioles, and capillaries; nephropathy; infection; digestive diseases; accidents; and suicide were 28.8, 18.5, 9.0, 10.5, 0.3, 4.8, 6.4, 7.9, 3.2, and 0.8%, respectively. CONCLUSIONS: Approximately 71.2% of the diabetes-related deaths would not be ascribed to diabetes on death certificates in Taiwan. The diabetic men have higher risk of dying than women, and diabetic patients have excess mortality when compared with the general population. For underlying causes of death not listed as diabetes, total cardiovascular death, including cardiopulmonary disease, stroke, and disease of arteries, arterioles, and capillaries, is the most common cause of death, followed by cancer.     

Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study.

OBJECTIVE: This population-based study, carried out in the framework of the Verona Diabetes Study, investigated mortality from specific causes in known type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A cohort of 7,148 known type 2 diabetic patients (3,366 men and 3,782 women) was identified on 31 December 1986 and followed up for 5 years (1987-1991). Underlying causes of death were obtained from death certificates and were coded according to the International Classification of Diseases, Ninth Revision. Cause-specific death rates of diabetic subjects were compared with those of the inhabitants of Verona. By 31 December 1991, 1,550 diabetic subjects (744 men and 806 women) had died. RESULTS: The standardized mortality ratio (SMR) for all causes of death was 1.42 (95% CI 1.35-1.50). The highest SMRs were for the following specific causes: diabetes (SMR 4.47 [3.91-5.10]), gastrointestinal diseases (1.83 [1.50-2.21])--particularly liver cirrhosis (2.52 [1.96-3.20])--and cardiovascular diseases (1.34 [1.23-1.44]), particularly cerebrovascular (1.48 [1.25-1.73]) and ischemic heart diseases (1.41 [1.24-1.62]). A significantly higher than expected risk of mortality for cardiovascular causes was already present in the first 5 years after diagnosis and decreased with age. Type 2 diabetic patients treated with insulin had a higher risk of dying than those treated orally or by diet. CONCLUSIONS: The highest SMRs in the diabetic cohort were for diabetes and liver cirrhosis. The mortality risk for cardiovascular diseases, although significantly higher than expected, was much lower in Italian type 2 diabetic patients than that reported for American patients. The evidence of an early effect on mortality suggests that prevention, early diagnosis, and treatment should be improved.     

Use of health services by diabetic persons. II. Hospital admissions

Over a 10-mo period, a computerized admission discharge system was scrutinized to identify all persons with diabetes mellitus admitted to a general hospital in Christchurch, North Canterbury (population 342,000), New Zealand. The 274 admissions by 197 diabetic persons (42% were insulin treated, 14% were newly diagnosed, 44% were non-insulin-dependent) contributed to 3.6% of the total hospital admissions, with duration of stay being longer than for nondiabetic persons (13.6 versus 11.3 days, P = 0.05). Patients admitted were aged 11-91 yr (mean 59 yr); those over 50 yr of age were numerically the largest admission group. Although cardiovascular illnesses were the most frequent events precipitating admission (34%), potentially preventable admissions for reasons of infection, poor glycemic control, or hypoglycemia were found in all age groups. Just under half of the 902 registered insulin-treated diabetic patients living in this health region had at some stage participated in diabetes education programs at the time this admission survey was undertaken. Of these, only nine were admitted. The other 70 insulin-treated patients admitted who lived in this region had never had diabetes education. Overall, only 11.7% of patients admitted had received diabetes education. These data show that, for insulin-treated diabetic individuals at least, admission rates were substantially lower among those who were sufficiently motivated to attend diabetes education programs.     

Patterns of insulin dependence in an African diabetic clinic.

Analysis of the age of onset of diabetes amongst insulin-treated patients in a large African diabetic clinic revealed a bimodal type of distribution, 23 per cent having an age of onset before 30 years and 77 per cent with onset at greater than or equal to 30 years of age. All 66 of the young insulin-treated group (21.7 +/- 4.8 years (mean +/- 1 SD)), and a random selection of 50 older insulin-treated patients (49.7 +/- 10 years), were studied. The older group were better controlled (HbA1 8.4 +/- 1.7 per cent vs. 10.8 +/- 2.6 per cent, p less than 0.001), on lower doses of insulin (49 +/- 23 vs. 71 +/- 23 u/day, p less than 0.001) and had higher body mass index (26.0 +/- 5.6 vs. 21.8 +/- 3.5, p less than 0.001). Serum C-peptide (0.24 +/- 0.15 vs. 0.07 +/- 0.10 nmol/l, p less than 0.0001), and C-peptide/glucose ratio (2.57 +/- 2.65 vs. 0.56 +/- 0.98 nmol/mmol x 10(2), p less than 0.001) were very significantly higher in older patients. Patients with later onset disease thus had better preservation of pancreatic function, higher body mass index and better glycaemic control on lower doses of insulin. These features suggest that older insulin-treated patients could in fact be 'Type 2' or non-insulin dependent patients, and the condition may be controllable with diet and/or oral hypoglycaemic agents, at least in some.     

Hospitalization among diabetic children and adolescents and the general population in Germany. German Working Group for Pediatric Diabetology

OBJECTIVE: To compare hospitalization in a multicenter-based cohort of diabetic children and adolescents (aged 1-19 years) in Germany with that of the general population. RESEARCH DESIGN AND METHODS: Based on standardized documentation, hospital stays after manifestation were ascertained in diabetic subjects 1-19 years of age in 1997. Hospitalization data in the general German population were derived from official statistics. Incidence rates and numbers of hospital days were estimated. Ratios of hospitalization incidences and numbers of hospital days between the diabetic and the general population were calculated. Costs for hospital care in the German diabetic population in 1997 were determined. RESULTS: A total of 5,874 patients came from 61 pediatric centers (52% male, age [mean +/- SD] 12.2 +/- 4.3 years, diabetes duration 4.6 +/- 4.4 years). Hospitalization incidence rates and hospital days per person-year (95% CI) were 0.27 (0.25-0.29) and 1.80 (1.75-1.84) in the diabetic population and 0.0948 (0.0946-0.0949) and 0.6416 (0.6412-0.6420) in the general population. The standardized ratio of hospital incidences was 3.1 (2.9-3.2), and the ratio of numbers of hospital days was 2.8 (2.7-2.9). Costs for hospital care after manifestation were estimated to be $506 (U.S. dollars) per person-year and $12.4 million in the whole German diabetic population aged 1-19 years in 1997; including hospital stays at diabetes onset, total annual costs were $24 million ($970 per person-year). CONCLUSIONS: Diabetic children and adolescents in Germany had an approximately three times higher hospitalization risk and three times more hospital days than the age-matched general population. Including hospitalization at diabetes onset, the annual costs of hospital care for the German diabetic population aged 1-19 years amounted to approximately 1% of all costs for hospital care in this age-group. Thus, costs were largely overproportional (diabetes prevalence 0.1%).     

Mortality in concurrent type 1 diabetes and anorexia nervosa

OBJECTIVE: Previous studies in this field report early occurrence of diabetic complications, but excess mortality, though expectable, has not been reported. We combined information from earlier studies to estimate the mortality for this group of patients. RESEARCH DESIGN AND METHODS: The observed mortality is analyzed using crude mortality rate (a percentage), standardized mortality ratio (SMR), incidence rate ratio, risk difference, and survival analysis. RESULTS: After approximately 10 years of follow-up, 13 of 510 females with type 1 diabetes, 43 of 658 females with anorexia nervosa (AN), and 8 of 23 concurrent case subjects had died. Mortality rate was 2.2 (per 1,000 person-years) for type 1 diabetes, 7.3 for AN cases, and 34.6 for concurrent cases. Crude mortality rates were 2.5, 6.5, and 34.8%, respectively. SMR was 4.06 in type 1 diabetes, 8.86 in AN, and 14.5 in concurrent cases. Survival analysis indicated between-group differences in mortality. CONCLUSIONS: Concurrent type 1 diabetes and AN is a rare but serious condition in females. All indexes of mortality evidence excess mortality in this preliminary study. Vigorous and well-directed treatment efforts seem vital for this subpopulation. Collaboration between diabetologists and eating disorder specialists is warranted. The implications of other eating disorders and subclinical eating disorders in diabetic populations need to be analyzed, especially because these conditions are more frequent than clinical eating disorders.     

Islet cell surface antibodies in diabetes and their possible influence on glucose tolerance

The prevalence of islet cell surface antibodies (ICSA) in patients with insulin-dependent (IDD), noninsulin-dependent (NIDD) or newly-diagnosed diabetes mellitus was studied. The antibodies were present in 14 (27%) of 15 IDD patients below the age of 30 years, and in 11 (12%) of 91 NIDD patients. Among 46 newly-diagnosed diabetic patients, (aged over 30 years), 14 (30%) were antibody-positive and had a fasting blood sugar exceeding 11 mmol glucose. The glucose tolerance after a standardized breakfast decreased in IDD or insulin-treated patients with ICSA compared to patients without antibodies. C-peptide was also lower in patients with circulating ICSA (xi CPR/xi BS during a standardized breakfast test 0.61 +/- 0.30 vs. 1.09 +/- 0.3 in IDD, 1.18 +/- 0.13 vs. 1.46 +/- 0.43 in the patients with insulin treatment). These results suggest that circulating ICSA be also present in some newly-diagnosed patients of over 30 years of age who require insulin treatment and who have an associated decreased glucose tolerance and C-peptide response.     

Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry.

OBJECTIVE: Our objective was to analyze the prevalence, incidence, and mortality of diabetes in a population of 280,539 inhabitants. RESEARCH DESIGN AND METHODS: The incidence, prevalence, and deaths from diabetes at all ages of a population have been prospectively followed in the county of Skaraborg, Sweden, since 1991. RESULTS: The annual incidence of diabetes per 100,000 inhabitants in 1991-1995 was (mean +/- 95% CI) 14.7 +/- 3.2 for type 1 diabetes (diagnosed at 24.1 +/- 2.2 years of age) and 265.6 +/- 16.1 for type 2 diabetes (diagnosed at 66.6 +/- 0.6 years of age). The incidence of type 2 diabetes was significantly (P < 0.001) higher among men. There was no significant change in the age at diagnosis of diabetes. Although the incidence rate and the age at diagnosis were constant, the prevalence of diabetes increased by 6% each year. The relative mortality risk for diabetic patients was almost four times higher than expected. The median age at death, however, increased significantly, from 77.2 to 80.2 years (P < 0.05), during the study. CONCLUSIONS: The prevalence but not the incidence rate of diabetes increased during the years 1991-1995. Although diabetic patients showed a high relative mortality, increased survival apparently explains the increase in prevalence of diabetes in the country of Skaraborg.     

A paracetamol-pasta test for assessing gastric emptying in healthy and diabetic subjects

Previous studies have shown that the relationship between gastrointestinal symptoms and gastric emptying is weak. Therefore the quantitative assessment of gastric emptying with a relatively simple, non-invasive test would be of considerable clinical value in insulin-treated diabetic patients to identify those with disturbed gastric emptying. The aim of this investigation was to evaluate the inter- and intra-subject variability of a paracetamol-pasta test in healthy subjects and in IDDM patients. Eighteen healthy subjects (8 women) with a mean age of 37 years (range 19-68) and 19 IDDM patients (10 women) with a mean age of 48 years (range 25-62) and mean duration of diabetes of 28 years (range 6-52) were studied on two occasions with an interval of 1 to 4 weeks. After an overnight fast the subjects ingested a standardized pasta meal mixed with 2 g paracetamol in a period of 15 min. Blood samples were drawn at regular intervals after meal intake and analysed for paracetamol (P) and blood glucose. The serum levels of P were significantly lower at 15 min in diabetic patients. The intra-subject coefficients of variation (CV%) of the areas under the serum paracetamol concentration-time curve (AUC) were almost identical in healthy and diabetic subjects, while the intra-subject CV of the P-Tmax was considerably lower in diabetic patients as well as markedly lower than the corresponding inter-subject CV. The inter-subject CVs of all parameters calculated were generally higher in diabetic patients. This study indicates that the assessment of paracetamol absorption kinetics during a paracetamol-pasta test is reproducible in healthy as well as in diabetic subjects. Diabetic patients with non-optimal glucose control and without a case history indicating gastroduodenal motor function disturbances achieve lower serum concentration of P at 15 min and generally display a higher inter-individual variability indicative of subclinical disturbances of gastric emptying in this group of patients.     

In-hospital mortality after acute myocardial infarction in patients with diabetes mellitus.

OBJECTIVES: To examine in-hospital mortality after acute myocardial infarction in patients with diabetes mellitus. METHODS: All patients in an 800-bed teaching hospital who had a discharge diagnosis of myocardial infarction, verified by creatine kinase levels at admission, between 1991 and 1993 made up the study population. All 118 such patients who died during this period made up the case group. Two control subjects (n = 236), survivors of the hospitalization, matched by sex, age, and length of hospitalization, were selected randomly for each case. Information on the presence of diabetes mellitus, medical history, and data related to myocardial infarction were obtained through retrospective chart review. RESULTS: The mean age of all subjects in the study was 76 years. Thirty-three percent of the patients in the case group and 31% of the control subjects had a history of diabetes mellitus (odds ratio = 1.04; 95% CI, 0.64-1.70), indicating that diabetes mellitus was not associated with an increased risk of in-hospital death. The adjusted odds ratio was 1.10 (95% CI, 0.48-2.51) in patients with non-insulin-treated diabetes mellitus and 0.80 (95% CI, 0.34-1.86) in insulin-treated patients. Multivariate analysis, with conditional logistic regression, confirmed that known prognostic factors for myocardial infarction, rather than diabetic status, are predictive of in-hospital mortality. CONCLUSIONS: Once the effects of age are accounted for, the risk of in-hospital mortality is not greater in patients with diabetes mellitus than in patients without diabetes; however, diabetes mellitus may be an important factor for long-term survival.     

Is leptin associated with diabetic retinopathy?

OBJECTIVE: In advanced stages of diabetic retinopathy, new blood vessels are formed based on undefined mechanisms. Recently, leptin was shown to possess an angiogenic action in vitro and to induce neovascularization in vivo. The aim of the present study was to investigate the relationship between plasma leptin levels and the severity of diabetic retinopathy. RESEARCH DESIGN AND METHODS: There were 70 patients with type 2 diabetes (age 47.9 +/- 9.7 years, BMI 26.4 +/- 3.3 kg/m2) who were seen in a retina outpatient clinic recruited and assigned to subgroups according to the stage of their diabetic retinopathy. There were 66 healthy volunteer subjects matched with the diabetic patients for age, BMI, and sex who served as control subjects (age 46.0 +/- 8.8 years, BMI 27.1 +/- 2.3 kg/m2). Fasting plasma leptin levels were measured. RESULTS: Plasma leptin level of the diabetic patients was not significantly different from the control subjects. In patients with proliferative diabetic retinopathy (n = 17), the mean plasma level of leptin (16.1 +/- 9.2 ng/ml) was significantly higher than that in patients with nonproliferative retinopathy (n = 20) (11.5 +/- 3.5 ng/ml, P = 0.039) or patients without retinopathy (n = 33) (5.8 +/- 3.7 ng/ml, P = 0.001). The mean leptin level in patients with nonproliferative diabetic retinopathy was also significantly higher than that in patients without retinopathy (P = 0.002). CONCLUSIONS: Our results show that the more advanced the diabetic retinopathy, the higher the plasma leptin levels, even after adjusting the leptin levels for BMI. The presence of such a positive correlation need not imply a causal relationship. Nevertheless, previously observed leptin-induced promotion of angiogenesis and neovascularization lends support to the possibility that leptin may play a role in the progression of human diabetic retinopathy to a proliferative phase. This possibility deserves further investigation.     

Mortality and predictors of mortality in a cohort of Brazilian type 2 diabetic patients

OBJECTIVE: To investigate mortality rates and predictors of mortality in Brazilian type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A prospective follow-up study was carried out with 471 type 2 diabetic outpatients. Primary end points were all-cause, diabetes-related, and cardiovascular deaths. Excess mortality in this cohort was evaluated by calculating standardized mortality ratios (SMRs) in relation to those of the Rio de Janeiro population. Predictors of mortality were assessed by Kaplan-Meier survival curves and by uni- and multivariate Cox survival analyses. RESULTS: During a median follow-up of 57 months (range 2-84 months), 121 (25.7%) patients died, 91 (75.2%) from diabetes-related causes and 44 (36.4%) from cardiovascular diseases. After adjusting for age and sex, the all-cause SMR was 3.36 (95% confidence interval [CI] 2.81-4.02) and the cardiovascular SMR was 3.28 (CI 2.44-4.41). In the Cox multivariate analysis, the predictors of mortality were older age, increased 24-h proteinuria, preexisting vascular disease, presence of frequent ventricular premature contractions and prolonged maximum heart rate-corrected QT interval on baseline electrocardiogram, and decreased serum HDL cholesterol. The use of beta-blockers was a protective factor. In Kaplan-Meier curves, these variables were capable of distinguishing subgroups of patients with significantly different prognoses. CONCLUSIONS: Brazilian type 2 diabetic patients had a more than threefold excess mortality than the general population, largely because of increased cardiovascular mortality risk. Several clinical, laboratory, and electrocardiographic predictors of mortality were identified that could possibly be modified to decrease the mortality burden of type 2 diabetes in Brazil.     

Periodontal disease and mortality in type 2 diabetes

OBJECTIVE: Periodontal disease may contribute to the increased mortality associated with diabetes. RESEARCH DESIGN AND METHODS: In a prospective longitudinal study of 628 subjects aged > or =35 years, we examined the effect of periodontal disease on overall and cardiovascular disease mortality in Pima Indians with type 2 diabetes. Periodontal abnormality was classified as no or mild, moderate, and severe, based on panoramic radiographs and clinical dental examinations. RESULTS: During a median follow-up of 11 years (range 0.3-16), 204 subjects died. The age- and sex-adjusted death rates for all natural causes expressed as the number of deaths per 1,000 person-years of follow-up were 3.7 (95% CI 0.7-6.6) for no or mild periodontal disease, 19.6 (10.7-28.5) for moderate periodontal disease, and 28.4 (22.3-34.6) for severe periodontal disease. Periodontal disease predicted deaths from ischemic heart disease (IHD) (P trend = 0.04) and diabetic nephropathy (P trend < 0.01). Death rates from other causes were not associated with periodontal disease. After adjustment for age, sex, duration of diabetes, HbA1c, macroalbuminuria, BMI, serum cholesterol concentration, hypertension, electrocardiographic abnormalities, and current smoking in a proportional hazards model, subjects with severe periodontal disease had 3.2 times the risk (95% CI 1.1-9.3) of cardiorenal mortality (IHD and diabetic nephropathy combined) compared with the reference group (no or mild periodontal disease and moderate periodontal disease combined). CONCLUSIONS: Periodontal disease is a strong predictor of mortality from IHD and diabetic nephropathy in Pima Indians with type 2 diabetes. The effect of periodontal disease is in addition to the effects of traditional risk factors for these diseases.     

Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy

OBJECTIVE: To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND METHODS: Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360-370 nm and 430-450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups. RESULTS: In the PDR group (11.9 +/- 3.9 arbitrary units [mean +/- SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 +/- 1.3 arbitrary units), the patients without DR (7.4 +/- 2.1 arbitrary units), and the patients without PDR (6.9 +/- 2.2 arbitrary units) (P < 0.05). CONCLUSIONS: We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.     

Red cell age-related changes of hemoglobins AIa+b and AIc in normal and diabetic subjects.

The minor hemoglobin components, hemoglobin AIa+b and hemoglobin AIc, were measured in the 10% youngest and 10% oldest erythrocytes of 15 normal and 14 diabetic subjects. Erythrocyte fractions were obtained by centrifugation in isopyknic concentrations of dextran: 28.5% of 40,000-mol wt dextran yeilded the 10% lightest of young cells, and 30.5% dextran provided the 10% heaviest or old erythrocytes. Both normal and diabetic erythrocytes contain increased amounts of Hb AIa+b and Hb AIc in old as compared to young cells. In normal subjects, young cells contained 1.2+/-0.2%, and old cells contained 1.8+/-0.4% Hb AIa+b. Corresponding values for diabetic cells were 1.7+/-0.6 and 2.6+/-0.9%. Hb AIc increased from 3.1+/-0.8 to 6.0+/-1.1% in normals and from 5.1+/-2.1 to 10.1+/-3.7% in diabetics. The results indicate that both cell age and diabetes are significant determinants of the amounts of Hb AIa+b and Hb AIc.     

Systolic time intervals and the QT-QS2 interval in young female diabetics

To detect subclinical cardiomyopathy in diabetic patients without evidence of coronary artery disease, systolic time intervals were measured in 51 insulin-treated young female diabetics (mean age 27 years and mean duration of diabetes 12 years) and in 15 healthy women of the same age. The ratio of the pre-ejection period to the left ventricular ejection time (PEP/LVET) was used as an index of left ventricular performance. The PEP/LVET ratio was normal in all diabetics and did not differ statistically from that in the control group. The electrical (QT) and electromechanical (QS2) systole were measured from the same high velocity recordings. The QT-QS2 interval (mean +/- SD) was shorter in the diabetic group (-16 +/- 22 ms vs. -33 +/- 9 ms, p less than 0.01). Ten diabetics but none of the healthy women, had the QT interval longer than the QS2. This was a result of both shortening of the QS2 and prolongation of the QT. In conclusion, our results suggest normal myocardial contractility in these young female diabetics. The significance and mechanism of the shortened QT-QS2 interval in the diabetics need further investigation.     

Elevated plasma asymmetric dimethylarginine as a marker of cardiovascular morbidity in early diabetic nephropathy in type 1 diabetes

OBJECTIVE: Increased plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been associated with endothelial dysfunction, insulin resistance, and atherosclerosis in nondiabetic populations. In end-stage renal failure, circulating ADMA is elevated and a strong predictor of cardiovascular outcome. This study investigated the relation between ADMA and diabetic micro- and macrovascular complications in a large cohort of type 1 diabetic patients with and without early diabetic nephropathy. RESEARCH DESIGN AND METHODS: ADMA concentrations in plasma were determined by a high-performance liquid chromatography method in 408 type 1 diabetic patients with overt diabetic nephropathy (252 men; mean age 42.7 years [SD 11.0], mean duration of diabetes 28 years [SD 9], median serum creatinine level 102 micromol/l [range 52-684]). A group of 192 patients with longstanding type 1 diabetes and persistent normoalbuminuria served as control subjects (118 men; mean age 42.6 years [SD 10.2], mean duration of diabetes 27 years [SD 9]). RESULTS: In patients with diabetic nephropathy, mean +/- SD plasma ADMA concentration was elevated 0.46 +/- 0.08 vs. 0.40 +/- 0.08 micromol/l in normoalbuminuric patients (P<0.001). An increase in plasma ADMA of 0.1 micromol/l increased the odds ratio of nephropathy to 2.77 (95% CI 1.89-4.05) (P<0.001). Circulating ADMA increased in nephropathy patients with declining kidney function, as indicated by elevated values in the lower quartiles of glomerular filtration rate (<76 ml.min(-1).1.73 m(-2)) (P<0.001 ANOVA). Mean ADMA levels were similar in patients with or without diabetic retinopathy (P>0.2). However, in 44 patients with nephropathy and history of myocardial infarction and/or stroke, ADMA was significantly elevated at 0.48 +/- 0.08 micromol/l compared with 0.46 +/- 0.08 micromol/l in patients without major cardiovascular events (P=0.05). CONCLUSIONS: Elevated circulating ADMA may contribute to the excess cardiovascular morbidity and mortality in early diabetic nephropathy.     

Effects of diet treatment on some biochemical and physiological parameters in patients with type 2 diabetes mellitus

The aim of the present study was to investigate the effect of diet treatment on serum glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein-(HDL) cholesterol, low density lipoprotein-(LDL) cholesterol and very low density lipoprotein-(VLDL) cholesterol levels, systolic and diastolic blood pressure and electrocardiograms (ECGs) in patients with type 2 diabetes mellitus (DM). Twenty healthy subjects (mean age 45.9 +/- 3.7 years) and newly diagnosed patients with type 2 diabetes prior to receiving diet treatment (mean age 47.6 +/- 6.2 years) were included in this study. Diabetic patients were given a standard dietary treatment that was composed of 50% to 55% carbonhydrate and 30% fat (1200 kcal for women and 1600 kcal for men) for 2 months. No diet treatment was applied for control. For both groups serum glucose, TG, TC, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol levels, systolic and diastolic blood pressure and ECGs were measured at the beginning and end of the diet treatment. Although diet treatment decreased the elevated serum glucose in diabetic patients, it still remained higher than that in the controls. Diet treatment also decreased the elevated TG and VLDL-cholesterol in diabetic patients to control values. Although heart rate and systolic blood pressure were higher, diastolic blood pressure was not different in diabetic patients than those in controls. Ventricular hypertrophy was also observed in ECGs of 10% of diabetic patients. Diet treatment normalized all of these findings, except systolic blood pressure. This study showed that diet treatment could not normalize the high systolic blood pressure in type 2 DM. Thus, an effective way of controlling blood pressure should be taken to improve healing in DM.     

Prevalence and characteristics of brittle diabetes in Britain

We investigated the prevalence and characteristics of 'brittle diabetes', defined as insulin-dependent diabetes mellitus associated with glycaemic instability of any type, leading to life disruption with recurrent and/or prolonged hospitalizations. A questionnaire was sent to all physicians and paediatricians running diabetic clinics in the UK, from lists held at the British Diabetic Association. A total of 414 brittle patients were reported (72% questionnaire return). Most were young (mean age +/- SD was 26 +/- 15 years), though there was a small peak at ages 60-70 years. There was an excess of females (66%) and overall clinic prevalence was 1.2 per 1000 diabetic patients and 2.9 per 1000 insulin-treated diabetic patients. On average, there was 1.0 brittle patient per diabetic clinic. The most common form of brittleness was recurrent ketoacidosis (59%), with 17% having predominant hypoglycaemia, and 24% mixed instability. Female excess was highest and mean age lowest in the recurrent ketoacidosis group, whilst the reverse was true for those with recurrent hypoglycaemia. Causes of brittleness were offered by 58% of consultants, and most (93%) considered various psychosocial problems as likely underlying factors. We conclude that brittle diabetes is a small but significant problem, currently affecting about 1 per 1000 diabetic patients. Most, but by no means all, are young females--often with recurrent ketoacidosis. Older age groups are more likely to have recurrent hypoglycaemic or mixed types of brittleness. Perceived causes of brittleness are usually psychosocial.      

An investigation into the effects of hypoglycaemia in young people aged 16–30 years

This study investigates the effects of hypoglycaemia on the working, social and personal lives of young people aged 16–30 years (mean age 23 9 years) who have insulin-treated diabetes mellitus A total of 52 questionnaires were returned from a sample size of 70 subjects Quantitative and qualitative analysis revealed that young people's lives are disrupted to varying degrees by hypoglycaemia Hypoglycaemia and the complications of diabetes were found to be a source of concern to the subjects in the study, although 19 (36 5%) rarely earned out any self-monitoring A more flexible approach to diabetic management is indicated, together with an agreed consensus of diabetic control between patients and professionals