Association of impaired glucose metabolism in morbid obesity with hypoadiponectinaemia.

BACKGROUND: Increased circulating levels of cytokines and chemokines and decreased adiponectin levels are associated with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). As obesity is the major risk factor for T2DM it is not clear why many patients with morbid obesity remain normoglycaemic and if this protection can be attributed to a lower grade of inflammation or higher adiponectin levels. MATERIALS AND METHODS: Glucose tolerance of morbidly obese patients (n=2 754, body mass index > or =40 kg/m2) was assessed by oral glucose tolerance tests. In a case-control design we compared levels of eight immune mediators and adiponectin from patients with IGT/T2DM (n=52) and normal glucose tolerance (NGT; n=59). Gene expression in peripheral blood was determined by quantitative RT-PCR, and serum concentrations of immune mediators and adiponectin were measured by ELISA and bead-based multiplex technology. RESULTS: About 54% of the patients in our morbidly obese cohort were normoglycaemic, while 14% were diagnosed with IGT and 32% with T2DM. There was no statistically significant difference in mRNA expression or serum levels of proinflammatory markers. Interestingly, we could demonstrate an association of NGT with higher adiponectin levels (p=0.039). Adiponectin levels were negatively correlated with interleukin (IL)-6 and macrophage chemoattractant protein (MCP)-1, but independent the other immune mediators. CONCLUSIONS: We found an association of lower adiponectin levels with IGT/T2DM, but no further increase in inflammatory markers in morbid obesity. This suggests that in addition to chronic, low-grade inflammation, adiponectin is an important factor in the development of, or protection against, T2DM in obesity.

Reliability of causes of death in persons with Type I diabetes.

AIMS/HYPOTHESIS: To compare causes of death assessed by a clinical review committee, the information given on death certificates, and ICD-codes provided by the State Documentation Office in deceased persons with Type 1 (insulin-dependent) diabetes mellitus. METHODS: A cohort of 3674 patients were monitored for 10+/-3 (mean +/- SD) years. Vital status and end-stage diabetic complications were documented for 97%; 251 patients had died. Causes of death were assessed by a clinical review committee and compared to the information provided by death certificates and ICD-9 codes. RESULTS: The review committee defined a leading cause of death in 94% of cases, whereas death certificates were available for 73% and ICD-codes for 79% of patients; 10% of death certificates could not be evaluated due to insufficient information. Diabetes was mentioned on 71% of death certificates, and renal disease in 75% of cases with renal replacement therapy. There was acceptable agreement between the committee, death certificates and ICD-codes only for deaths due to neoplasma, and between the committee and death certificates for deaths due to acute myocardial infarction, cerebrovascular events and accidents. In only one out of four deaths due to hypoglycaemia and in four of seven deaths due to ketoacidosis was this diagnosis mentioned on the death certificate. No death due to hypoglycaemia or ketoacidosis and 41% due to suicide were identifiable by ICD-codes. CONCLUSION/INTERPRETATION: Reliance on death certificates or ICD-codes as the only sources of information on the cause of specific mortality does not provide data of sufficient reliability for evaluation of clinical outcome in Type I diabetes.

Predictors of mortality and end-stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy.

AIMS: To assess predictors of mortality and end-stage diabetic complications in patients with Type 1 diabetes mellitus on intensified insulin therapy. METHODS: A cohort of 3,674 patients (insulin treatment before age 31) who had participated in a 5-day in-patient group treatment and teaching programme for intensification of insulin therapy between 9/1978 and 12/1994 were reassessed after 10 +/- 3 (mean +/- SD) years. RESULTS: Vital status and data on blindness, amputations, and renal replacement therapy were documented for 97% patients; 7% patients had died, 1.3% had become blind, 2% had amputations and 4.6% started renal replacement therapy. Using the Cox proportional hazards model, the following risk factors of mortality as assessed at baseline were identified: nephropathy (at least macroproteinuria), hazard ratio 3.8 (95% confidence interval 2.6-5.6); smoking, 1.9 (1.4-2.6); diabetes duration, 1.5 (1.2-1.8) for a difference of 10 years; serum cholesterol, 1.1 (1.0-1.2) for a difference of 1 mmol/l; lower social status, 1.4 (1.1-1.8) for a difference of 1 out of 3 levels; age, 1.3 (1.1-1.6) for a difference of 10 years; male sex, 1.4 (1.1-1.9); systolic blood pressure, 1.1 (1-1.2) for a difference of 10 mmHg. For the combined endpoint - blindness or amputations or renal replacement therapy - predictors were: nephropathy, foot complications, HbA1c, smoking, cholesterol, systolic blood pressure, retinopathy, hypertension, and social status. CONCLUSION: In Type 1 diabetic patients who start intensified insulin therapy, nephropathy remains the strongest predictor of mortality and end-stage complications. Glycosylated haemoglobin is a risk factor of end-stage complications but not of mortality. Conventional risk factors comparable to the general population, particularly smoking become operative as predictors of both mortality and end-stage complications.

Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy.

OBJECTIVE: To study the prognosis of persons with type 1 diabetes in relation to the degree of nephropathy at initiation of intensified insulin therapy. DESIGN: Ten years follow-up of a cohort of 3674 patients who had participated in a 5-day group treatment and teaching programme for intensification of insulin therapy between September 1978 and December 1994. SETTING: Ten diabetes centres in Germany. SUBJECTS: A total of 3674 patients (insulin treatment before age 31), age at baseline 27 +/- 10 years, with a diabetes duration of 11 +/- 9 years. Patients were divided into three groups according to baseline renal parameters (group I, normal proteinuria, n = 1829; group II, microproteinuria, n = 1257; group III, at least macroproteinuria, n = 367). MAIN OUTCOME MEASURES: End-stage diabetic complications (blindness, amputations, renal replacement therapy, standardized mortality ratios (SMR) and causes of death. RESULTS: Outcome measures were documented for 97% of patients; 251 (7%) had died. During follow-up, 1% of patients in group I, 4% in group II and 47% in group III had at least one end-stage diabetic complication. SMR for men: nephropathy group I, 2.2 (95% CI = 1.5-3); group II, 3.2 (2.3-4.3); group III, 11.5 (8.8-14.7). SMR for women: group I, 2.5 (1.5-3.8); group II, 3.5 (2.2-5.3); group III, 27 (19.8-35.9). Causes of death for men and women combined: group I (total 58 deaths)--cardiovascular, 21 (36%); hypoglycaemia, 1; ketoacidosis, 3; violent deaths, 17 (29%); others, 16; group II (66 deaths)--cardiovascular, 25 (38%); hypoglycaemia, 2; ketoacidosis, 2; violent deaths, 14 (21%); others, 23; group III (114 deaths)--cardiovascular, 68 (60%); hypoglycaemia, 2; ketoacidosis, 5; infections, 15 (13%); violent deaths, 5 (4%); others, 19. CONCLUSIONS: Patients with microproteinuria have only a slightly worse prognosis than patients with normal proteinuria during the first 10 years after initiation of intensified insulin therapy. Excess mortality amongst patients who started intensified insulin therapy is mainly due to those with manifest clinical nephropathy.

Injection-meal interval: recommendations of diabetologists and how patients handle it.

Because regular insulin does not lower blood glucose immediately after injection many physicians recommend an injection-meal interval (IMI). By asking patients to inject well before beginning a meal, these physicians hope to compensate for the lag time between the injection of insulin and its onset of action. The aim of our study was to find out what physicians recommend to their patients with respect to the IMI, when prescribing intensive insulin therapy. A total of 58 diabetologists were surveyed by means of a structured questionnaire. A fixed IMI of 15 (0-30) min [median (range)] was recommended by 29% of the 58 diabetologists, and a flexible IMI was recommended by 71%. The minimal interval for the suggested flexible IMI was 0 min and the maximal interval 45 min (median 23 min). We compared these results with findings of 192 patients with Type 1 diabetes from a population based study. In this study patients were asked by questionnaire about their daily life handling of the IMI. Among the group of 134 patients reporting use of a flexible IMI, 62% used an IMI of < or = 15 min, 16% one of 20-25 min, and 21% one of > or = 30 min. There were 12 patients using a flexible IMI who adapted it so frequently that they could not state a typical interval. A total of 58 patients (30%) used a fixed IMI (67% used an IMI of < or = 15 min, 7% one of 20-25 min, 26% one of > or = 30 min). Our surveys show that diabetologists advocating intensive insulin therapy usually recommend an IMI shorter than 30 min. The majority of patients (75%) with Type 1 diabetes use an IMI of < 30 min in daily life.

Risk factors of severe hypoglycaemia in adult patients with Type I diabetes--a prospective population based study.

The objective of this study was to identify possible risk factors of severe hypoglycaemia (SH) in a prospective population based study of adult Type I (insulin-dependent) diabetic patients. A representative sample of 684 patients (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years), living in the district of Northrhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. A comprehensive baseline assessment of possible predictors of SH included sociodemographic and disease related variables, hypoglycaemia awareness, diabetes management, and attitudes and behavioural aspects as expressed by the patients. After a mean of 19 +/- 6 months 669 (98%) patients were interviewed about events of SH since the baseline examination. Using the multiple Cox proportional hazards model, five risk factors of SH were identified: SH during the preceding year [hazard ratio (HR) 2.7, 95% confidence intervals (CI) 1.8-4.2], any history of SH (HR 1.9, CI 1.1-3.4), C-peptide negativity (HR 4.0, CI 1.2-12.7), social status (HR 0.8 for a difference of 5 units for a value range of 0-24, CI 0.6-0.9), and patients' determination to reach normoglycaemia (HR 0.7 for a difference of 1 unit for a value range of 1-6, CI 0.5-0.9), indicating that the lower the social status and the higher the patients' determination to reach normoglycaemia, the higher the risk of SH. After eliminating the history of hypoglycaemia from the model, impaired hypoglycaemia awareness and patients' inappropriate denial of SH as their particular problem became additional significant risk factors of SH. In conclusion, in this population based study of adult Type I diabetic patients, C-peptide negativity, a previous event of SH, patients' determination to reach normoglycaemia and social class were risk factors of SH.

Social status and the quality of care for adult people with type I (insulin-dependent) diabetes mellitus--a population-based study.

UNLABELLED: The objective of this study was to assess the degree of diabetes care and education achieved for Type I (insulin-dependent) diabetes mellitus at the community level in relation to social status and to elucidate potential pathways that mediate any social class gradient. A population-based sample of 684 adults with Type I diabetes (41% women, mean +/- SD age 36 +/- 11, diabetes duration 18 +/- 11 years) in the district of North-Rhine (9.5 million inhabitants), Germany, were examined in their homes using a mobile ambulance. RESULTS: HbA1c (normal 4.3-6.1%) 8.0 +/- 1.5%, incidence of severe hypoglycaemia (injection of glucose or glucagon) 0.21 cases per patient-year; 62% of patients had participated in a structured group treatment and teaching programme for intensification of insulin therapy; 70% used 3 or more insulin injections per day, 9% were on continuous subcutaneous insulin infusion; 91% reported to have had measurements of HbA1c during the preceding year, and 80% to have had an examination of the retina by an ophthalmologist. Care was insufficient with respect to the quality of blood pressure control (70% of patients on antihypertensive drugs had blood pressure values > or = 160/95 mmHg), patient awareness of proteinuria/albuminuria (27% of patients had not heard about it) and prevention of foot complications (only 42% with a diabetes duration over 10 years had remembered to have a foot examination during the preceding 12 months). There was a pronounced social gradient with respect to micro- and macrovascular complications (prevalence of overt nephropathy 7 vs 20% for highest vs lowest quintiles of social class [OR 3.5, 95% CI 1.6-7.5, p = 0.002]) and diabetes-specific quality of life. HbA1c, blood pressure and smoking accounted for part of the association between social class and microvascular complications. The social class gradient was not due to inequality to access to health services, but to lower acceptance among low social class patients of preventive and health maintaining behaviour. In conclusion, achieved standards of care are high with respect to the implementation of intensified treatment regimens, the level of patient education achieved, treatment control and eye care, whereas areas for improvement are blood pressure control and preventive measures for foot care. A substantial social gradient in diabetes care persists despite equal access of patients to health services.

Validation of a diabetes-specific quality-of-life scale for patients with type 1 diabetes.

OBJECTIVE: To validate a diabetes-specific quality-of-life scale and to assess its psychometric properties in a large sample of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: To assess the quality of diabetes care in a population-based study, a representative sample of 684 patients with type 1 diabetes was examined. A total of 657 patients (42% female; mean age 36 years; mean diabetes duration 18 years) completed the diabetes-specific quality-of-life scale (DSQOLS), which comprised 64 items on individual treatment goals (10 items), satisfaction with treatment success (10 items), and diabetes-related distress (44 items). Statistical examinations covered factor analysis, internal consistency of subscales, and construct and discriminant validity. RESULTS: Factor analysis of the 44 items on diabetes-specific burdens revealed six reliable components (Cronbach's alpha): social relations (0.88), physical complaints (0.84), worries about future (0.84), leisure time flexibility (0.85), diet restrictions (0.71), and daily hassles (0.70). All six subscales were significantly correlated with a validated well-being scale (r = -0.35 to -0.53, P < 0.001) and treatment satisfaction (r = 0.28 to 0.43, P < 0.001). Physical complaints (r = 0.24) and worries about future (r = 0.17) showed the highest correlations with HbA1c (P < 0.001). A flexible insulin therapy, a liberalized diet, the absence of late complications, and a higher social status were significantly associated with more favorable scores in different domains. CONCLUSIONS: The DSQOLS is a reliable and valid measure of diabetes-specific quality of life. The scale is able to distinguish between patients with different treatment and dietary regimens and to detect social inequities. Use of the DSQOLS for assessment of individual treatment goals as defined by the patients may be helpful to identify motivational deficits and to tailor individual treatment strategies.

Cigarette smoking and progression of retinopathy and nephropathy in type 1 diabetes.

The objective of the present study was to analyse the association between cigarette smoking and progression of retinopathy and nephropathy, respectively, in a prospective multicentre study including 636 people with Type 1 diabetes: 81% of the original cohort of consecutively referred patients, aged 15 to 40 years and free of severe late diabetic complications. At baseline, all patients had participated in a 5-day in-patient group treatment and teaching programme for intensification of insulin therapy. Patients were examined at recruitment, and after 1, 2, 3 and 6 years including assessment of smoking status, blood pressure, metabolic control, and degree of nephropathy. Degree of retinopathy was assessed by ophthalmoscopy or fundus photography at baseline and after 6 years. Several logistic regression analyses were performed by describing the responses retinopathy and nephropathy, respectively, either as progression yes/no or as actual status at the 6-year follow-up and by using different measures for smoking. Adjustments for important covariables were made. While significant associations between smoking, and retinopathy and nephropathy respectively, were found, the relations were variable depending on the statistical model used. The results show that the real associations between smoking and retinopathy and nephropathy are complex and that more emphasis should be put on the complete description of the response variables and the statistical models used in clinical and epidemiological research.

Liberalized diet in patients with type 1 diabetes.

OBJECTIVE: To document that strict dietary regimen are not necessary in the context of intensified insulin therapy. DESIGN: German multicentre, prospective cohort study; 6 years follow-up. SETTING: Ambulatory examination using a mobile ambulance. SUBJECTS: A total of 636 type 1 diabetic patients (age 33 +/- 7 years, diabetes duration 15 +/- 7 years; mean +/- SD), who had participated in a structured, 5-day, in-patient, group treatment and teaching programme for intensification of insulin therapy and liberalization of the diabetes diet 6 years prior to follow-up. MAIN OUTCOME MEASURES: Relations between the extent to which patients practise a liberalized diet, the degree of metabolic control (HbA1c, severe hypoglycaemia, body mass index, cholesterol), and the patients' perceived burden through dietary treatment. RESULTS: In the total patient group, HbA1c was 7.9 +/- 1.6%, and the incidence of severe hypoglycaemia was 0.17 cases per patient during the preceding year; 31% patients injected insulin < or = 3 times per day, 58% 4-7 times per day, and 11% used insulin pump therapy. Only 11% patients reported following a meal plan, whereas 89% continually changed timing and amount of carbohydrate intake; only 5% had the same number of meals every day, whereas as many as 20% varied the number of meals per day by four or more; 53% skipped main meals; 85% habitually consumed sugar or sugar containing foods. Patients with a higher degree of diet liberalization injected insulin or used an insulin pump therapy more frequently, and perceived their dietary treatment to be less burdensome. No clinically significant associations were found between the extent of diet liberalization and metabolic control. CONCLUSIONS: Under the conditions where type 1 diabetic patients have the opportunity to participate in an intensified insulin treatment and teaching programme, liberalization of the diabetes diet is not associated with adverse effects on glycaemic control, but is associated with less perceived burden through dietary treatment.