Improved metabolic control results in better myogenic response of retinal arterioles in patients with diabetes mellitus type 1.

AIMS: The retina is protected against high blood pressure by the myogenic constriction of arterioles (the Bayliss effect). Hyperglycemia impairs this retinal autoregulation by endothelial dysfunction. The purpose of this prospective pilot study was to test whether improved metabolic control results in a measurable effect on the myogenic response of human retinal arterioles to acute increases in blood pressure. METHODS: The Bayliss effect was measured in 25 patients with diabetes mellitus by the Retinal Vessel Analyzer (RVA), both before and after participation in a treatment and teaching program for intensified insulin therapy with the goal of improved metabolic control. After 12 months, 17 subjects still fulfilled the inclusion criteria and underwent an identical measurement. The Wilcoxon test was used for statistical analysis. RESULTS: During the first session, a rise in mean arterial pressure (MAP) of 20.2 +/- 8.6 mm Hg was followed by an arterial vasoconstriction of -3.2 +/- 2.9%. The educational program resulted in a significant drop in Hb(A1c) levels (9.4 +/- 1.9 vs. 6.9 +/- 0.98%). Eight subjects did not meet the inclusion criteria after 12 months. Seventeen subjects were remeasured and a rise in blood pressure of 19.5 +/- 9.9 mm Hg in the second session was associated with a significantly improved arterial vasoconstriction of -5.9 +/- 2.7% (session I vs. session II, p = 0.006). CONCLUSION: The myogenic response of the arterial wall in human retinal arterioles was significantly improved by the therapeutic intervention.

Flexible, intensive insulin therapy and dietary freedom in adolescents and young adults with Type 1 diabetes: a prospective implementation study.

AIMS: To assess the outcome of a Diabetes Treatment and Teaching Programme (DTTP) on glycated haemoglobin (HbA1c), severe hypoglycaemia (SH) and severe ketoacidosis (SKA) in adolescents and young adults with Type 1 diabetes. METHODS: Quality-assurance project with assessment of participants 1 year after participation in a DTTP (5-day inpatient course, groups < or = 10 patients, fixed curriculum of education/training, introduction of dietary freedom). Before-after analyses of participants aged 12-15, 15-18, 18-21 and 21-24 years. Main outcome measures were HbA1c, SH and SKA. RESULTS: For the 1592 participants, aged 12 to 24 years, mean age at enrolment was 19 +/- 3 years, mean duration of diabetes was 7.3 +/- 5.4 (range 0.3-24) years, mean baseline HbA1c declined from 8.8 +/- 2.3% to 8.1 +/- 2.0%. The incidence of SH was 0.31 vs. 0.11 events/patient/year; the incidence of SKA 0.17 vs. 0.07 events/patient/year. In mixed effects models taking into account effects of centres, age and diabetes duration, the mean difference was -0.64%[P < 0.001, 95% confidence interval (CI) -0.79 to -0.5] for HbA1c, -0.2 events/patient/year (P < 0.0001, 95% CI -0.28 to -0.12) for SH and -0.1 events/patient/year (P < 0.0001, 95% CI -0.14 to -0.06) for SKA. CONCLUSIONS: Adolescents and young adults with Type 1 diabetes benefit from participation in a standard DTTP for flexible, intensive insulin therapy and dietary freedom.

[A 64-year-old female patient with recurring hypoglycaemia. Difficult aspects of diagnosis]. / 64-jährige Patientin mit rezidivierenden Hypoglykämien. Schwierige Diagnosestellung.

Insulinomas are the most common pancreatic islet cell tumours and are characterised by uncontrolled insulin secretion even in the presence of hypoglycaemia. Diagnosis is usually made by the detection of endogenous hyperinsulinism over a period of fasting. We report the case of a patient with insulinoma without hyperinsulinaemia. A secretion and overexpression of split insulin has to be discussed. The diagnosis was made by endoscopic ultrasound-guided fine-needle aspiration and the immunohistochemical detection of chromogranine. In conclusion, the present report demonstrates that insulinomas should be considered and searched for in every case of hypoglycaemia, even when associated with normal insulin levels. It also confirms the essential role of endoscopic ultrasonography in the diagnosis of insulin-secreting tumors.

Prevalence of impaired glucose tolerance 6 years after gestational diabetes.

AIM: Prevalence of glucose metabolism disorders in women six years after gestational diabetes in the index pregnancy (GDM). METHOD: 227 Caucasian women who developed GDM between 1995 and 1996 were investigated; 173 women (BMI 27.5+/-6.0 kg/m2) received 75 g oGGT on average 5.8+/-2.0 years after delivery. RESULTS: Impaired glucose metabolism was found in 31.2%, IGT or IFG 19.1%, diabetes mellitus type 2 (DM2) 9.2%, diabetes mellitus type 1 (DM1) 2.3%, second GDM 0.6%. 27.2% (BMI 25-29.9 kg/m2) were overweight, 23.1% suffered from obesity (BMI 30-39.9 kg/m2) and 5.2% morbid obesity (BMI>or=40 kg/m2). In comparison to a healthy control group, women with DM2 at re-examination were: older in age (32.1+/-5.9 vs. 29.1+/-4.8 years, p<0.05), had higher BMI (29.4+/-6.9 vs. 24.6+/-4.8 kg/m2, p<0.05), higher fasting blood glucose (6.5+/-1.9 vs. 5.2+/-0.9 mmol/l, p<0.05), earlier diagnosis of GDM (25+/-8 vs. 29+/-5 SSW, p<0.05), more frequent insulin therapy during pregnancy (75 vs. 24%) and had significantly higher insulin- and C-peptide for all measures of the oGTT, whereas HbA1c was not different (4.9+/-0.5 vs. 4.8+/-0.3%, n. s.). CONCLUSION: In an average of 5.8 years after the diagnosis of GDM, the majority of women still have chronic insulin resistance. One third has either IGT, IFG or diabetes mellitus. Therefore, a long term follow-up is strongly recommended for women diagnosed with GDM.

Structured diabetes therapy and education improves the outcome of patients with insulin treated diabetes mellitus. The 10 year follow-up of a prospective, population-based survey on the quality of diabetes care (the JEVIN Trial).

AIMS/HYPOTHESIS: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year follow-up, population-based survey of all insulin treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of implementation of the St. Vincent Declaration and to evaluate the effect of recent changes in the health care system and new treatment strategies. PATIENTS AND METHODS: 190 patients (83% of the target population), 244 patients (90%) and 261 patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively. RESULTS: Up to 1994/95, the HbA1c of patients with type 1 diabetes mellitus increased (1994/95: 8.50+/-1.80% versus 1989/90: 7.83+/-1.60%, p=0.002). For patients with type 2 diabetes mellitus, it remained constant (9.01+/-2.06% versus 9.17+/-1.60%, n. s.). During the period from 1994/95 to 1999/2000, there was a substantial improvement in the relative HbA1c of both, patients with type 1 (7.62+/-1.55%, p<0.0001), and with type 2 diabetes (7.57+/-1.29%, p<0.0001). Up to 1999/2000, 87.7% of the patients with type 1 (1989/90: 0%, 1994/95: 73.2%) and 96.6% of the patients with type 2 diabetes (1989/90: 0%, 1994/95: 89.7%) participated in TTP's. The incidence of acute and the prevalence of long-term complications remained constant. CONCLUSIONS: Results of the population-based, prospective trial to optimise patients' quality of diabetic control suggest: For patients with insulin treated type 2 diabetes mellitus, excellent treatment can be available by primary care physicians interested, educated and highly engaged in diabetes therapy. Moreover, structured diabetes therapy consisting of treatment and teaching programmes, regular self-monitoring, patients' insulin dose adjustment and patients' empowerment, should be offered to all patients with diabetes mellitus.

[Alopecia totalis, hypotension and erectile dysfunction in a 34 year old patient. Difficult clarification of a common cause]. / Alopecia totalis, Hypotonie und erektile Dysfunktion bei einem 34-jährigen Mann. Schwierige Klärung einer gemeinsamen Ursache.

The occurrence of both autoimmune endocrinopathies and endocrinopathies caused by other reasons is called polyglandular autoimmune syndrome (PAS-syndrome). In a 34 years old man with weakness, weight loss and erectile dysfunction we found low cortisol caused by an autoimmune adrenalitis and low testosterone caused by a hypophysitis with impaired gonadotropin secretion. Thyroid autoantibodies and islet cell autoantibodies without any hormone deficiencies were further signs of a broad endocrine autoimmune syndrome. In the following 11 years the patient developed three autoimmune disorders: paradrenal glandular insufficiency, hypogonadism caused by hypophysitis, Diabetes mellitus type 1. In the same time several non endocrine autoimmune diseases became manifest: alopecia totalis, vitiligo, retrobulbar neuritis and keratoconjunctivitis.

Perinatal morbidity in women with undiagnosed gestational diabetes in northern thuringia in Germany.

INTRODUCTION: Undiagnosed gestational diabetes mellitus (GDM) is associated with severe perinatal complications. PATIENTS AND METHODS: Out of 970 women, infant and maternal morbidity was assessed in 114 mother-children-pairs with an infant birth weight over the 90th percentile (Voigt et al., 1996). It was the aim of this retrospective study to assess the number of mothers with undiagnosed GDM, who have born a macrosomic child. RESULTS: The macrosomia rate in newborns was 12 % in this study excluding macrosomic infants of mothers with preexisting diabetes mellitus. Maternal data: Age 28.3 +/- 5.3 years, adipositas (body-mass-index > 30 kg/m) in 42.1 % vs. 30.4 % in the peer group (p < 0.02), increase in weight > 15 kg during pregnancy in 57.9 % of the mothers who have given birth to a macrosomic child vs. 30.9 % in the peer group (p < 0.0001), family history of diabetes mellitus (28.0 % vs. 11.3 % in the peer group, p = 0.006), preeclampsia in 8.8 % vs. 2.7 % in the peer group (p = 0.002), cervical insufficiency in 2.6 % vs. 0.4 % in the peer group (p = 0.02). After delivery HbA1c was elevated in 38.6 % of the women having born macrosomic infant (mean HbA1c: 5.0 % +/- 0.5). Infant data: neonatal jaundice 16.7 % vs. 4.5 % in the peer group, p < 0.0001. There were no statistically significant differences concerning perinatal condition and malformations. Neonatal hypoglycaemia occurred in 9.6 % of the macrosomic infants. Cord blood insulin levels were significantly elevated in comparison to the peer group of mothers without metabolic disorders and having born eutroph infants (8.4 mU/l [3.0 - 100.0] vs. 5.3 mU/l [3.0 - 30.7], p = 0.01). 11.4 % of all macrosomic infants had cord blood insulin levels above the normal range. CONCLUSION: More than one third of the mothers having born one or more macrosomic infants had an impairment of glucose metabolism immediately after birth. The elevated prevalence of preeclampsia in this group confirms the relationship of hypertension and impaired glucose metabolism during pregnancy. The detection of hyperinsulinaemia, postnatal hypoglycaemia, elevated prevalence of neonatal jaundice with need of further therapy and diabetic fetopathy in macrosomic infants of mothers, whose metabolism was not monitored during pregnancy, pinpoint the need for a diagnostic screening for GDM.

A transmembrane protein-tyrosine phosphatase receptor type C (CD45) exon A point mutation (77 C to G) is not associated with the development of type 1 diabetes mellitus in a German population.

To investigate whether a C to G transversion at position 77 in exon A of the CD45 gene is associated with the development of diabetes mellitus type 1 (T1D), we studied 165 patients and 220 control individuals. The frequency of the 77G allele in the control group was 1.1%, which was not significantly different from the 1.2% found in the patient group (P = 0.922). The C to G transversion does not seem to be associated with susceptibility for T1D.

Population-based measurement of quality of diabetes care using HbA1c values in the state of Thuringia/Germany.

INTRODUCTION/HYPOTHESIS: There remains insufficient knowledge about the quality of diabetes therapy regarding structure, process and outcome given by primary care in Thuringia, and elsewhere in Germany. The project assesses a means of determining the quality of diabetes therapy in primary care by analysis of HbA1c values within a broad territory. METHODS: HbA1c tests of Thuringian patients were analysed by 20 participating medical laboratories between January 1 and March 31, 2002; each HbA1c test was identified by the postal code of the Thuringian General Practitioner (GP) who ordered the test and adjusted by a standardisation procedure (mean normal of healthy subjects 5 %). The German state of Thuringia (population of 2,421,871) consists of 23 urban and rural districts. This format was also used in the present study. RESULTS: Twenty participating laboratories contributed 59,702 HbA1c tests from diabetic patients in Thuringia. Adjusted mean HbA1c of entire Thuringia: 6.75 %, 36.4 % of all HbA1c tests were above 7.0 % and 3,0 % of all HbA1c values above 10.0 %. Regional percentage of HbA1c tests above 7.0 % ranged between 28.2 % and 47.3 %. Regional percentage of HbA1c tests above 10.0 % ranged between 1.8 % and 4.8 %. Subgroup analyses comparing urban vs. rural districts showed significantly lower mean HbA1c (6.72 % vs. 6.75 %, CI 0.01 - 0.06, p < 0.01) and percentage of HbA1c tests above 7 % (8.19 % vs. 8.24 %, CI 0.01 - 0.08, p < 0.01) in urban areas. CONCLUSIONS: Mean HbA1c as an indicator of glycaemic control of diabetes patients in primary care in Thuringia was good. The percentage of patients who need immediate medical intervention to prevent acute complications varied between districts, which is indicative for differences in quality of diabetes care in Thuringia. However, the proposed method is still experimental and has not yet been evaluated. Consequently, considerable bias might influence the results.

Insulin pump therapy in patients with Type 1 diabetes mellitus: results of the Nationwide Quality Circle in Germany (ASD) 1999-2000.

BACKGROUND AND AIMS: Only a few specialised centres in Germany initiated insulin pump therapy before 1990. Initiation of pump therapy involves the participation in a structured treatment and teaching programme (TTP). During the last decade insulin pump therapy has been widely used. The impact of this decentralisation on the quality of care is still unknown. The aim of this trial was both to evaluate the outcome of insulin pump therapy outside specialised centres and to identify features that might be associated with persistently increased HbA1 c levels. PATIENTS AND METHODS: 250 patients with type 1 diabetes mellitus (age 36.0 +/- 13.1 years; diabetes duration 16.1 +/- 9.9 years), who were on continuous subcutaneous insulin infusion (CSII) therapy during 1999 - 2000, were individually included in the study. Second examination was performed one year after participation in the in-patient TTP for insulin pump therapy. Patients were recruited from 21 member institutions of the Working Group for Structured Diabetes Therapy of the German Diabetes Association. Further details were sought by questionnaire on those patients with persistently increased HbA1c (> 1.7 fold of mean normal range.) RESULTS: One year after participation in the TTP for CSII relative HbA1c (original value/mean normal of the local method [Müller et al., 1999]) decreased from 1.51 (0.9 - 3.2) to 1.44 (0.9 - 3.6) (p < 0.0001), severe hypoglycaemia from 0.46 to 0.12/patient/year (p < 0.001), severe ketoacidosis from 0.08 to 0.05/patients/year (p = 0.003) and hospitalisation from 5.2 to 3.1 days/patient/year (p = 0.002). In 43/207 (17%) the incidence of severe hypoglycaemia was unchanged (before 0.12 and after TTP 0.14/patients/year), there was slight increase in severe ketoacidosis (before 0.15; after TTP 0.23/patients/year) and hospitalisation days were unchanged (before 4.5; after TTP 4.4 days/patients/year). The following factors were associated with adverse outcomes: psychological problems including eating disorders and alcohol abuse (28%), lack of interest in self-management (28%) and social problems (11%). In 28% there was no follow-up treatment by diabetologists specialised in pump therapy. CONCLUSION: The benefits of insulin pump therapy are improvement of HbA1c, reduction of hypoglycaemia, ketoacidosis and hospitalisation days as well as improved flexibility. It is possible to draw up a list of clinical criteria and service requirements, which are likely to reduce failures.

[Autoregulation of retinal arterioles in patients with diabetes mellitus and normal probands]. / Autoregulation retinaler Arteriolen bei Patienten mit Diabetes mellitus und Normalprobanden.

BACKGROUND: Measurement of myogenic autoregulation of retinal arterioles was demonstrated by the use of the Retinal-Vessel-Analyzer (Carl Zeiss, Jena). The purpose of the presented study was to find a significant difference of this myogenic response in a group of healthy individuals vs. a group of patients with pathologic conditions. PATIENTS AND METHODS: As a group of patients with known pathology in microcirculation patients with type 1 diabetes were chosen. By isometric exercise an identical rise in mean arterial blood-pressure was provoked in 20 patients with type-1 diabetes and 20 matched healthy volunteers. The myogenic response of retinal arterioles was measured in both groups by the use of the Retinal-Vessel-Analyzer. The Wilcoxon test was used for statistical analysis within the two groups whereas both groups were compared with each other by the use of the Mann-Whitney test. RESULTS: Having the same age and same blood-pressure rise (p = 0.624) a significant better myogenic response was found in the healthy subjects vs. the diabetic group (p = 0.008). In the diabetic group no correlation was found between myogenic response and duration of diabetes (p = 0.982) or HbA1c values (p = 0.83). CONCLUSIONS: In this study significant loss of autoregulation in patients with type 1 diabetes is demonstrated. By the use of the Retinal-Vessel-Analyzer noninvasive testing of the function of autoregulation of retinal arterioles is possible. This method might prove to be of great value in early detection of diabetic vessel pathology.

Should insulin therapy in type 2 diabetic patients be started on an out- or inpatient basis? Results of a prospective controlled trial using the same treatment and teaching programme in ambulatory care and a university hospital.

The aim of this study was to determine whether Type 2 diabetic patients should be hospitalised to start insulin therapy. The same structured diabetes treatment and teaching programme (DTTP) was used in outpatients in 10 private practices after postgraduate training of physicians and teaching staff as well as in the Diabetes Department of the University Hospital of Jena, Germany. Seventy-two consecutive Type 2 diabetic patients (ambulatory group) participated in the outpatient DTTP. After one year, 70 patients were re-evaluated and compared with 70 other patients (matched pairs) who were referred to the University Hospital of Jena to start insulin treatment and participated in the same programme during hospitalisation. Initially there were no significant differences between the groups for age, gender, HbA1c, body mass index (BMI), and the time since diagnosis of diabetes. HbA1c (mean normal value 5%) decreased in both groups within the 12 months of follow-up (ambulatory group from 10.3 +/- 2.2 to 8.1 +/- 1.7, p < 0.0001; inpatient group from 10.4 +/- 1.6 to 8.4 +/- 1.7, P = 0.0001). At follow-up there were no significant differences between the groups concerning insulin dosage, HbA1c, severe hypoglycaemia, BMI, and hospitalisation. In combination with a DTTP, the initiation of insulin therapy on an ambulatory basis was as safe and effective as in the inpatient programme. Cost-benefit analysis demonstrated substantial savings in direct costs in the ambulatory programme.

[Flare measurement and albuminuria in type I diabetics]. / Flaremessung und Albuminurie bei Typ-I-Diabetikern.

BACKGROUND: Chronic hyperglycaemia causes microangiopathy with manifestations in different organ systems. The purpose of this study was to investigate whether anterior chamber protein concentrations and albuminuria in patients with diabetes mellitus type 1 have any correlation. PATIENTS AND METHODS: 23 patients with type 1 diabetes were examined in both eyes by the use of the laser flare-cell meter (LFCM). After clinical exclusion of urinary tract infection urine-samples were taken on the examination-day. Patients were divided into two groups: group 1 consisted of 13 patients with albuminuria (8x microalbuminuria, 5x macroalbuminuria), group 2 comprised 10 controls with normal urine albumin concentrations. RESULTS: Both groups were identical according to age and gender. The flare values in the group with albuminuria were significantly elevated (10.7 +/- 7.1 counts/msec) in comparison to those of the control group (3.7 +/- 1.9 counts/msec)(p = 0.042). The duration of the diabetes was as well significantly different in both groups (7.9 +/- 6.9 yrs. vs. 23.9 +/- 13.4 yrs.)(p = 0.02). A correlation was found between albuminuria and flare values (r = 0.67; p = 0.003). CONCLUSIONS: Our results demonstrate a correlation between protein concentration in aqueous and albuminuria. In future flare measurements could possibly offer a non-invasive diagnosis of diabetic nephropathy.

The JEVIN trial: a population-based survey on the quality of diabetes care in Germany: 1994/1995 compared to 1989/1990.

Since 1990 in most Eastern European countries health care systems have been decentralized or are undergoing the processes of decentralization. Increasingly, diabetic patients are no longer treated by diabetologists but by non-specialized physicians. During the same period structured treatment and teaching programmes have been introduced and health care is increasingly influenced by the St. Vincent declaration. To show the effect of these changes on the quality of diabetes care 90% (n = 244) of all insulin-treated diabetic patients aged 16 to 60 years and living in the city of Jena (100247 inhabitants) were studied in 1994/1995. The results were compared with the baseline examination of 1989/1990 (n = 190). HbA1c (HbA1c/mean normal) in IDDM patients under specialized care was similar in 1994/1995 (1.54 +/- 0.27, n = 47) to 1989/1990 (1.52 +/- 0.31, n = 131, p = 0.0018), but higher under non-specialized care (1.71 +/- 0.38, n = 80, p = 0.0087). In the total group of NIDDM patients there was no significant change in HbA1c (1994/1995: 1.75 +/- 0.4, n = 117, vs 1989/1990: 1.78 +/- 0.4, n = 59, p = 0.67), but with a tendency to higher HbA1c under non-specialized (1.81 +/- 0.4, n = 79) compared to specialized care (1.66 +/- 0.39, n = 38, p = 0.06). Incidence of severe hypoglycaemia (IDDM 0.13; NIDDM 0.04), ketoacidosis (0.02; 0.01) and the prevalence of nephropathy (21%; 35%) and neuropathy (24%; 38%) remained unchanged in comparison to 1989/1990, whereas there was an increase in the prevalence of diabetic retinopathy. Specialized care is mandatory for patients with IDDM.

Endogenous plant hormones of the broad bean, Vicia faba L. (-)-jasmonic acid, a plant growth inhibitor in pericarp.

(-)-Jasmonic acid was identified as a plant growth inhibitor of the pericarp of Vicia faba by means of gas-liquid chromatography, high resolution mass spectrometry, (1)H-nuclear magnetic resonance ((1)H-NMR), and (13)C-NMR. Additionally, the pericarp contains very small amounts of abscisic acid (ABA) and 4'-dihydrophaseic acid. The highest level of jasmonic acid was reached prior to full pericarp length. This amount (3 µg g(-1) fresh weight) is similar to the maximal ABA content in the developing seed. Jasmonic acid is a plant growth inhibitor possessing a relative activity in the wheat seedling bioassay of 1-2.5%, compared to ABA. Contrary to ABA, jasmonic acid does not cause retardation of leaf emergence. The possible physiological role of jasmonic acid in the pericarp is discussed and compared with the assumed function of ABA in developing seeds.