C Kloos

Diabetic foot syndrome and renal function in type 1 and 2 diabetes mellitus show close association

BACKGROUND Diabetic nephropathy and diabetic foot syndrome (DFS) are two major complications of diabetes. Surprisingly, little is known of a potential relationship between renal function and the development of DFS in patients with preterminal renal insufficiency. A retrospective cohort study at a single tertiary university centre caring for a large collective of patients with type 1 and 2 diabetes was performed. Patients and methods. All patients with type 1 or 2 diabetes from 1989 to 2007 on the electronic patient sheet who had standardized food examination, albuminuria and serum creatinine were analysed. A total number of 899 patients with type 1 and 4007 individuals with type 2 diabetes were studied. Estimated glomerular filtration rate (eGFR) was calculated according to the modified equation 7 MDRD formula. Patients were grouped into the chronic kidney disease (CKD) stages according to the eGFR and presence of albuminuria. DFS was classified according to Wagner as well as Armstrong stages. RESULTS Forty-six patients (5.1%) of 899 patients with type 1 diabetes have active or a history of DFS. Patients with type 1 diabetes and DSF had significantly higher serum creatinine levels, lower eGFR, higher systolic blood pressure and higher HbA1c levels compared to those without DFS. There was a significant negative correlation between eGFR and the presence of DFS in patients with type 1 diabetes (r = -0.155, P < 0.01). In type 1 diabetes patients, there was a significant negative correlation (Spearman test) between eGFR and Wagner stages (r = -0.218, P = 0.01) as well as Armstrong stages (r = -0.255, P = 0.01). Multiple logistic regression analysis revealed a significant association between the presence of DFS and eGFR (odds ratio 0.696 per 10 ml/min increase, 95% confidence interval 0.627-0.773, P < 0.001). A total of 532 type 2 patients from 4007 patients had DFS (13.7%). Compared with type 2 patients without DFS, those with DFS were significantly older (P < 0.005), exhibited a higher HbA1c, had a longer duration of diabetes (P < 0.005), higher serum creatinine levels (P < 0.005) and a lower eGFR (P < 0.005). There was a significant negative correlation between the Wagner stages and eGFR (r = -0.104, P < 0.01) as well as Armstrong stages and eGFR (r = -0.125, P < 0.01) in all patients with type 2 diabetes (Spearman test). Multiple logistic regression analysis revealed a significant association between the presence of DFS and eGFR (odds ratio 0.873 per 10 ml/min increase, 95% confidence interval 0.842-0.904, P < 0.001). There were also significant associations between DFS and duration of diabetes as well as diastolic blood pressure. In addition, the Jonckheere-Terpstra test confirmed the decrease of eGFR with increasing Wagner and Armstrong stages in patients with type 2 diabetes. Smoking was not associated with a higher prevalence of DFS in type 1 and 2 diabetic patients. CONCLUSION There was a strong association between the degree of renal function impairment and DFS in this observational study. Data show that diabetics with DFS undergo a higher incidence of amputation; thus, it should be recommended that diabetic patients with renal insufficiency should be regularly screened for the presence of DFS.

Randomized Crossover Study to Examine the Necessity of an Injection-to-Meal Interval in Patients With Type 2 Diabetes and Human Insulin

OBJECTIVE Patients with diabetes and insulin therapy with human insulin were usually instructed to use an interval of 20–30 min between the injection and meal. We examined the necessity of the injection-to-meal interval (IMI) in patients with type 2 diabetes mellitus (T2DM) and flexible insulin therapy with human insulin. RESEARCH DESIGN AND METHODS In this randomized, open crossover trial, 100 patients with T2DM (47% men, mean age = 66.7 years) were randomized to the IMI first group (phase 1, IMI 20 min; phase 2, no IMI) or IMI last group (phase 1, no IMI; phase 2, IMI 20 min). The main outcome measures were HbA1c, blood glucose profile, incidence of hypoglycemia, quality of life, treatment satisfaction, and patient preference. RESULTS Forty-nine patients were randomized to the IMI first group and 51 patients to the IMI last group. Omitting the IMI only slightly increases HbA1c (average intraindividual difference = 0.08% [95% CI 0.01–0.15]). Since the difference is not clinically relevant, a therapy without IMI is noninferior to its application (P < 0.001). In the secondary outcomes, the incidence of mild hypoglycemia also did not differ between no IMI and IMI significantly (mean of differences = −0.10, P = 0.493). No difference in the blood glucose profile of both groups was found. Treatment satisfaction increased markedly, by 8.08, if IMI was omitted (P < 0.001). The total score of the quality of life measure did not show differences between applying an IMI or not. Insulin therapy without IMI was preferred by 86.5% of patients (P < 0.001). CONCLUSIONS An IMI for patients with T2DM and preprandial insulin therapy is not necessary.

Evaluation of a treatment and teaching refresher programme for the optimization of intensified insulin therapy in type 1 diabetes.

OBJECTIVE Evaluation of an ambulatory diabetes teaching and treatment refresher programme (DTTP) for the optimization of intensified insulin therapy in patients with type 1 diabetes (refresher course). METHODS 85 outpatients took part in this prospective multicentre trial. Metabolic and psychosocial data were analyzed at baseline (V1), 6 weeks (V2) and 12 months after DTTP (V3). RESULTS In patients with baseline HbA1c>7% (88%), HbA1c decreased by 0.36% (p=0.004). The percentage of patients with HbA1c≤7% increased from 21.3 to 34.9% and with HbA1c above 10% decreased from 6.6 to 1.6% at V3. The incidence of hypoglycaemia decreased significantly: non severe hypoglycaemia from 3.31 to 1.39 episodes/pat/week (p=0.001) and severe hypoglycaemia from 0.16 to 0.03 episodes/pat/year (p=0.02). The treatment satisfaction increased by +10 of maximal ±18 points. The negative influence of diabetes on quality of life decreased from -1.93 to -1.69 points (p=0.031). CONCLUSION In a group of patients with moderately controlled diabetes type 1 who were already treated with intensified insulin therapy, metabolic control, treatment satisfaction and quality of life were improved after participation in an ambulatory DTTP without increasing insulin dosage, number of injections or insulin species. PRACTICE IMPLICATIONS This DTTP is effective for the optimization of intensified insulin therapy.

Hemoglobin Concentrations Are Closely Linked to Renal Function in Patients with Type 1 or 2 Diabetes Mellitus

Background/Aims: It has been reported that anemia is more common in patients with diabetes mellitus, and that it occurs early in the disease process. Methods: In this study, we evaluated hemoglobin (Hb) values of patients with diabetes type 1 or 2 from a large collective receiving care from a tertiary center. A total of 751 patients with type 1 diabetes and 3,306 patients with type 2 were studied. Correlations were calculated for Hb with the following parameters: metabolic control (HbA1c and blood glucose), renal function [estimated glomerular filtration rate (eGFR), serum creatinine, albuminuria, proteinuria], blood leukocytes, duration of diabetes and use of ACE inhibitors/AT1-receptor antagonists. Results: 17% of patients with type 1 diabetes and 14% of those with type 2 had anemia [defined as an Hb <8.5 mmol/l (<13.68 g/dl) in men and <7.5 mmol/l (<12.07 g/dl) in women). There was a close positive correlation between Hb and eGFR, and a negative correlation with albuminuria and proteinuria. These close associations were also confirmed with linear regression analysis. A significant negative correlation was observed between serum creatinine levels and Hb. There was no negative correlation between actual Hb and mean HbA1c in the individual follow-up periods. No correlation was found between blood glucose (morning and postprandial blood glucose) and Hb. Blood leukocyte numbers, as a parameter of systemic inflammation, were not correlated with Hb. The use of ACE inhibitors/AT1-receptor antagonists had no adverse effect on Hb in our study cohort. Conclusion: No negative effects of metabolic control on Hb could be demonstrated in this study.

Flexible intensive versus conventional insulin therapy in insulin-naive adults with type 2 diabetes: an open-label, randomized, controlled, crossover clinical trial of metabolic control and patient preference.

Improving metabolic control can reduce complications in type 2 diabetes (1–4). Conventional insulin therapy (CIT) and flexible intensive insulin therapy (FIT) are treatment options in insulin-dependent type 2 diabetic patients. In CIT, participants inject premixed human insulin (30% regular insulin, 70% NPH insulin) before breakfast and dinner and follow individually adjusted diet plans with fixed amounts of carbohydrates (5). In FIT, human regular insulin is adjusted before main meals according to current blood glucose readings and desired carbohydrate intake. When necessary, NPH insulin is added at bedtime. CIT can be easy to handle and requires less active diabetes self-management. In FIT, patients benefit from dietary freedom and improvement in quality of life (6). In pilot studies, FIT has shown good metabolic control and low risk of hypoglycemia (7). FIT may have additional advantages due to better postprandial blood glucose control (8). We tested the hypothesis that FIT and CIT in insulin-naive adults with type 2 diabetes are equally effective in regard to metabolic outcomes. We hypothesized that younger participants, in employment, would prefer FIT. The trial was designed as a clinical, prospective, randomized, open-label, single-center, crossover study. The primary end point was glycosylated hemoglobin A1c (GHb); secondary end points were mild and severe hypoglycemia, insulin dosage, blood pressure, BMI, and therapy preference. Participants started insulin therapy either with CIT (group A) or FIT (group B), randomly. Individual insulin dosage and carbohydrate intake were determined …

Cognitive Function Is Not Associated With Recurrent Foot Ulcers in Patients With Diabetes and Neuropathy

OBJECTIVE To study whether there is an association between cognitive impairment and the relapse rate of foot ulcers in diabetic patients and those with previous foot ulcers. RESEARCH DESIGN AND METHODS This single-center prospective study assessed the association of cognitive function and risk for ulcer relapse in 59 patients with diabetes (mean age 65.1 years, diabetes duration 16.5 years, and A1C 7.4%), peripheral neuropathy, and a history of foot ulceration. Premorbid and current cognitive functions were measured (multiple-choice vocabulary test [Lehrl], number-symbol test, mosaic test [HAWIE-R], and trail-making tests A and B [Reitan]). Prevalence of depression was evaluated retrospectively (diagnoses in patient files or use of antidepressive medication). Patients were re-examined after 1 year. RESULTS Three patients (5%) died during follow-up (one of sepsis and two of heart problems). The remaining 56 patients (48%) developed 27 new foot ulcerations (78% superficial ulcerations [Wagner stage 1]). Characteristics of patients with and without ulcer relapse were not different. In a binary logistic regression analysis, cognitive function is not predictive of foot reulceration. CONCLUSIONS Cognitive function is not an important determinant of foot reulceration.

Improvement of HbA1c and stable weight loss 2 years after an outpatient treatment and teaching program for patients with type 2 diabetes without insulin therapy based on urine glucose self-monitoring

Objective Long-term outcomes after participation in a structured diabetes treatment and teaching program (DTTP) for patients with diabetes without insulin use, primarily based upon postprandial urine glucose self-monitoring (UGSM). Methods A total of 126 patients took part in the DTTP in a university outpatient department in 2004–2005. We re-evaluated 119 (94.4%) at baseline and at 6 months, 12 months, and 24 months. Hemoglobin A1c (HbA1c) was DCCT adjusted. Results HbA1c decreased significantly 6 months after education from 7.33% (±1.59%) to 6.89% (±0.98%; P = 0.001 versus baseline) and was maintained for up to 12 months (7.02% ± 1.07%; P = 0.017 versus baseline) as well as up to 24 months (6.96% ± 1.06%; P = 0.005 versus baseline). Weight decreased from 92.5 kg at baseline to 90.3 kg at 24 months (P = 0.014). A total of 36.5% of patients not on insulin therapy preferred UGSM, whereas 23.5% preferred blood glucose monitoring, at 24 months. Glucose control was similar in both groups at 24 months (HbA1c UGSM 7.03 versus blood glucose monitoring 6.97%; P = 0.807). Conclusion Participation in the DTTP resulted in long-term behavior modification. HbA1c of patients without insulin met the target 24 months after the DTTP, irrespective of the type of glucose self-monitoring.

Combined en-bloc liver-pancreas transplantation in patients with liver cirrhosis and insulin-dependent type 2 diabetes mellitus.

We report about our experience with combined en-bloc liver-pancreas transplantation in 14 patients with liver cirrhosis and insulin dependent type 2 diabetes mellitus. Exocrine drainage was achieved by duodeno-duodenostomy. Median posttransplant follow-up is currently 92.5 months. All patients were rendered independent from insulin therapy shortly after transplantation. Levels of glycosylated hemoglobin normalized in all recipients. Mean fasting C-peptide values increased from pretransplant 7.0±1.7 ng/mL to 10.5±2.9 ng/mL 3 months posttransplantation (P<0.001). One recipient (7.1%) developed recurrent exogenous insulin dependence 7 years after transplantation. Pancreas allograft rejection was confirmed by endoscopic biopsy of donor duodenum mucosa in two patients (14.3%). Calculated 5- and 7-year survival is currently at 64.3% and 64.3%, respectively. Our results indicate that combined en-bloc liver-pancreas transplantation using duodeno-duodenostomy is technically feasible and leads to excellent long-term control of glucose metabolism in patients with liver cirrhosis and insulin-dependent type 2 diabetes.

Prevalence of polyglandular autoimmune syndrome in patients with diabetes mellitus type 1

ZusammenfassungHintergrund und Ziel:Bei Patienten mit Diabetes mellitus Typ 1 treten gehäuft weitere endokrine Autoimmunerkrankungen (AIEK) auf. In dieser Studie wurden die Häufigkeit pathologischer Autoantikörper-(AAK-)Befunde und das Auftreten einer klinisch manifesten endokrinen AIEK (Hypophysitis, Adrenalitis, Thyreopathie, Perniziosa, Sprue) bei Patienten mit Diabetes mellitus Typ 1 im Verlauf 1 Jahres untersucht.Patienten und Methodik:Bei 139 Patienten mit Diabetes mellitus Typ 1 (Alter 44 ± 14 Jahre; Diabetesmanifestationsalter 26 ± 15 Jahre; Diabetesdauer 18 ± 12 Jahre; Body-Mass-Index 26 ± 4 kg/m2; HbA1c 7,5% ± 1,1% [Normalbereich 4,4–5,9%]), die in einer Universitätsklinik behandelt wurden, erfolgten ein AAK-Screening und bei pathologischem AAK-Titer eine Diagnostik hinsichtlich o.g. AIEK. Eine Befundkontrolle wurde 1 Jahr später durchgeführt.Ergebnisse:2003 zeigten 63% der Patienten mit Diabetes mellitus Typ 1 mindestens einen pathologischen AAK-Titer (2004: 60%) Bei 32% waren erhöhte AAK-Titer klinisch nicht relevant. Bei 31% der Patienten lag 2003 neben dem Typ-1-Diabetes mindestens eine weitere therapiepflichtige AIEK vor (2004: +3,6%): Dabei zeigten 22,3% zwei AIEK (2004: +2,2%) und 8,6% ≥ 3 AIEK (2004: +1,5%). Folgende positive AAK-Titer/Erkrankungsprävalenzen lagen vor (Vergleich 2004): positive Schilddrüsen-AAK: 47,5% (–0,7%)/Autoimmunthyreoiditis 24,5% (+2,8%) bzw. Morbus Basedow 4,3% (+0,7%), Nebennierenrinden-AAK 0,7% (+1,5%)/Morbus Addison 1,4% (±0), Gliadin-AAK bzw. Gewebsglutaminase-IgA positiv: 18,7% (–5,0%)/Sprue 1,4% (+0,8%), Parietalzellantikörper positiv: 15,8% (+7,2%)/Perniziosa 7,2% (+1,4%), Hypophysitis 0,7% (±0), Hypogonadismus 0,7% (±0). Alle Neuerkrankungen 2004 zeigten bereits im Vorjahr einen mindestens zehnfach erhöhten AAK-Titer. Zwischen Patienten mit versus ohne polyglanduläres Autoimmunsyndrom (PAS) fanden sich keine signifikanten Unterschiede bezüglich Alter (43 ± 14 vs. 46 ± 13 Jahre), Diabetesdauer (17 ± 13 vs. 18 ± 12 Jahre) und HbA1c (7,3% ± 0,9% vs. 7,6% ± 1,1%).Schlussfolgerung:In dieser Untersuchung wies mehr als die Hälfte der Patienten mit Diabetes mellitus Typ 1 mindestens einen weiteren pathologischen AAK-Titer auf, der jedoch keinen sicheren Rückschluss auf eine klinisch relevante AIEK zuließ. Bei 31% der Patienten lag mindestens eine weitere therapiepflichtige AIEK vor (Prävalenzanstieg um 3,6% innerhalb 1 Jahres). Bei Patienten mit Diabetes mellitus Typ 1 sollte an ein PAS gedacht werden. Eine Thyreopathie war am häufigsten und zeigte einen Prävalenzanstieg um 3,5% innerhalb 1 Jahres.AbstractBackground and Purpose:The aim of this study was to examine the prevalence of autoimmune antibodies (autoimmune hypophysitis, adrenalitis, thyropathy, pernicious anemia, celiac disease) and clinically relevant endocrine autoimmune disease (AIEK) in patients with type 1 diabetes in the course of 1 year.Patients and Methods:Antibody screening was performed in 139 diabetic patients (age 44 ± 14 years; years since diagnosis 26 ± 15 years; duration of diabetes 18 ± 12 years; body mass index 26 ± 4 kg/m2; HbA1c 7.5% ± 1.1% [normal range 4.4–5.9%]) who completed a routine clinic visit in 2003. Patients with pathologically increased antibody titers were further examined regarding the clinically relevant AIEKs. Reexamination was performed 1 year later.Results:In 2003, 63% of diabetic patients showed at least one pathologically increased antibody titer (2004: 60%). In 32% of the patients, increased antibody titers were clinically inapparent. Apart from diabetes mellitus type 1, in 2003, 31% suffered from other AIEK requiring therapy (2004: +3.6%): 22.3% harbored two additional AIEKs (2004: +2.2%) and 8.6% even ≥ 3 AIEKs (2004: +1.5%). The following pathologically increased antibody titers/prevalences of clinically relevant AIEKs were found (in comparison with 2004): increased antithyroid autoantibodies: 47.5% (–0.7%)/autoimmune thyroiditis 24.5% (+2.8%) and Graves’ disease 4.3% (+0.7%), respectively; adrenal cortex autoantibodies 0.7% (+1.5%)/Addison’s disease 1.4% (±0), gliadin peptide antibodies and IgA to tissue transglutaminase, respectively: 18.7% (–5.0%)/celiac disease 1.4% (+0.8%), parietal cell antibodies: 15.8% (+7.2%)/pernicious anemia 7.2% (+1.4%), hypophysitis 0.7% (±0), hypogonadism 0.7% (±0). All new AIEK manifestations in 2004 had had an at least tenfold increased antibody titer in 2003. Comparing patients with and without polyglandular autoimmune syndrome (PAS), no difference in age (43 ± 14 vs. 46 ± 13 years), duration of diabetes (17 ± 13 vs. 18 ± 12 years), and HbA1c (7.3% ± 0.9% vs. 7.6% ± 1.1%) could be found.Conclusion:In this study, more than half of the patients with diabetes mellitus type 1 had at least one pathologically increased antibody titer apart from diabetes without clinical sign of an additional AIEK. 31% of patients with increased antibodies presented with symptoms of another AIEK (increase by 3.6% within 1 year). Patients with diabetes mellitus type 1 should be screened for other AIEKs. Thyropathy had the greatest prevalence and increased by 3.5% within 1 year’s time.

Mortality and its Causes in a German Cohort with Diabetes Mellitus Type 1 after 20 Years of Follow-Up: The JEVIN Trial

BACKGROUND The JEVIN trial started as a cross-sectional study in 1989/90 in Jena. After a follow-up of more than 20 years, the mortality incidence of JEVIN participants with type 1 diabetes was surveyed. METHODS 103 (78.6%) of the 131 JEVIN patients participating at baseline could be examined. 38 persons (36.9%) had deceased. All JEVIN survey data and routine examinations documented in the electronic patient record EMIL® of surviving and deceased participants were used for analyses. We compared the data of the surviving with the deceased participants (follow-up time: 2,166 person-years). RESULTS The incidence rate of death was 1.75/100 person-years. Median observation time for all patients was 23.1 years (range 0.61-26.6 years). Mean age at death was 58.5 years (34.2-78.4 years), and diabetes duration 35 years (3.5-68.5 years). Most frequent causes of death were: cardiovascular diseases (48.2%, n=13) and infections (25.9%, n=7). There were no differences in age (p=0.302), diabetes duration (p=0.371), BMI (p=0.535), blood pressure (p=0.622/0.820), gender (p=0.566), and smoking status (p=0.709) between surviving and deceased persons. The mean HbA1c of the last year before death or last visit was higher in the deceased than surviving persons (7.5% vs. 7.0%; p=0.010). 57.4% of the surviving and 87.0% of the deceased participants had nephropathy (p=0.012), 79.7% vs. 89.7% retinopathy (p=0.241) and 61.4% vs. 63.3% neuropathy (p=0.860), but only nephropathy was significantly associated with increased mortality risk (HR=4.208, CI:1.226-14.440; HR=2.360, CI:0.696-8.004; HR=0.944, CI:0.436-2.043). CONCLUSIONS In the JEVIN population with diabetes mellitus type 1 only, diabetic nephropathy was associated with higher mortality risk.