Insulintherapie bei Typ-2-Diabetes: ein Review vom «Wann» übers «Wie» bis zum «Warum»

Der progressive Charakter des Typ- 2-Diabetes mellitus führt in vielen Fällen nach Ausschöpfen der oralen antidiabetischen Therapie zum Einsatz von Insulin. Insulin kann aber durch- aus auch in der Frühphase direkt nach Diabetesdiagnose oder intermittierend bei Verschlechterung der glykämischen Kontrolle im Rahmen von Infekten oder Medikamenteneinnahmen (wie z.B. Kortison) hilfreich und indiziert sein. Auf jeden Fall stellt die Insulintherapie keine Einbahnstrasse dar und kann gerade in diesen Fällen durchaus auch wieder sistiert werden. Der Beginn einer Insulintherapie soll eher vorsichtig mit einer bedarfsmässigen Anpassung im Verlauf erfolgen. Diese Anpassung kann nach entsprechender Schulung durchaus auch durch den Patienten selbst erfolgen.

GoCARB: Smartphone-App zur Kohlenhydratberechnung bei Typ-1-Diabetes

Smartphone-App zur Kohlenhydratberechnung Neue Technologien wie Blutzuckersensoren und moderne Insulinpumpen prägten die Therapie des Typ-1-Diabetes (T1D) in den letzten Jahren in wesentlichem Ausmaß. Smartphones sind aufgrund ihrer rasanten technischen Entwicklung eine weitere Plattform für Applikationen zur Therapieunterstützung bei T1D. GoCARB Hierbei handelt es sich um ein zur Kohlenhydratberechnung entwickeltes System für Personen mit T1D. Die Basis für Endanwender stellt ein Smartphone mit Kamera dar. Zur Berechnung werden 2 mit dem Smartphone aus verschiedenen Winkeln aufgenommene Fotografien einer auf einem Teller angerichteten Mahlzeit benötigt. Zusätzlich ist eine neben dem Teller platzierte Referenzkarte erforderlich. Die Grundlage für die Kohlenhydratberechnung ist ein Computer-Vision-gestütztes Programm, das die Mahlzeiten aufgrund ihrer Farbe und Textur erkennt. Das Volumen der Mahlzeit wird mit Hilfe eines dreidimensional errechneten Modells bestimmt. Durch das Erkennen der Art der Mahlzeiten sowie deren Volumen kann GoCARB den Kohlenhydratanteil unter Einbeziehung von Nährwerttabellen berechnen. Für die Entwicklung des Systems wurde eine Bilddatenbank von mehr als 5000 Mahlzeiten erstellt und genutzt. Resümee Das GoCARB-System befindet sich aktuell in klinischer Evaluierung und ist noch nicht für Patienten verfügbar.

Addressing schemes of self-monitoring of blood glucose in type 2 diabetes: a European perspective and expert recommendation

Self-monitoring of blood glucose (SMBG) in type 2 diabetes has increasingly been shown to display beneficial effects on glycemic control. SMBG is not only associated with a reduction of hemoglobin A1c but has also been demonstrated to increase patients' awareness of the disease. SMBG has also the potential to visualize and predict hypoglycemic episodes. International guidelines by the International Diabetes Federation, the European Society of Cardiology, and the European Association for the Study of Diabetes and also the International Society for Pediatric and Adolescent Diabetes emphasize that SMBG is an integral part of self-management. More recently, two European consensus documents have been published to give recommendations for frequency and timing of SMBG also for various clinical scenarios. Recently, a European expert panel was held to further facilitate and enhance standardized approaches to SMBG. The aim was to present simple, clinically meaningful, and standardized SMBG strategies for type 2 diabetes. The panel recommended a less intensive and an intensive scheme for SMBG across the type 2 diabetes continuum. The length and frequency of SMBG performance depend on the clinical circumstances and the quality of glycemic control. The expert panel also recommended further evaluation of various schemes for SMBG in type 2 diabetes in clinical studies.

Metabolomics reveals attenuation of the SLC6A20 kidney transporter in nonhuman primate and mouse models of type 2 diabetes mellitus

To enhance understanding of the metabolic indicators of type 2 diabetes mellitus (T2DM) disease pathogenesis and progression, the urinary metabolomes of well characterized rhesus macaques (normal or spontaneously and naturally diabetic) were examined. High-resolution ultra-performance liquid chromatography coupled with the accurate mass determination of time-of-flight mass spectrometry was used to analyze spot urine samples from normal (n = 10) and T2DM (n = 11) male monkeys. The machine-learning algorithm random forests classified urine samples as either from normal or T2DM monkeys. The metabolites important for developing the classifier were further examined for their biological significance. Random forests models had a misclassification error of less than 5%. Metabolites were identified based on accurate masses (<10 ppm) and confirmed by tandem mass spectrometry of authentic compounds. Urinary compounds significantly increased (p < 0.05) in the T2DM when compared with the normal group included glycine betaine (9-fold), citric acid (2.8-fold), kynurenic acid (1.8-fold), glucose (68-fold), and pipecolic acid (6.5-fold). When compared with the conventional definition of T2DM, the metabolites were also useful in defining the T2DM condition, and the urinary elevations in glycine betaine and pipecolic acid (as well as proline) indicated defective re-absorption in the kidney proximal tubules by SLC6A20, a Na(+)-dependent transporter. The mRNA levels of SLC6A20 were significantly reduced in the kidneys of monkeys with T2DM. These observations were validated in the db/db mouse model of T2DM. This study provides convincing evidence of the power of metabolomics for identifying functional changes at many levels in the omics pipeline.

Type 2 diabetes is associated with reduced ATP-binding cassette transporter A1 gene expression, protein and function

Objective Increasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ). Methods and Results Leukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, p<0.001; rho = −0.34, p = 0.006 respectively) and was reduced in Type 2 diabetes (T2DM) (p = 0.03). Leukocyte ABCA1 protein was lower in T2DM (p = 0.03) and positively associated with plasma HDL cholesterol (HDL-C) (rho = 0.34, p = 0.02). Apolipoprotein-A1-mediated cholesterol efflux correlated negatively with fasting glucose (rho = −0.50, p = 0.01) and positively with HDL-C (rho = 0.41, p = 0.02). It was reduced in T2DM compared with controls (p = 0.04). These relationships were independent of LXRα and PPARγ expression. Conclusions ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT.

Adipocytokines, hepatic and inflammatory biomarkers and incidence of type 2 diabetes. the CoLaus study

Context There is contradictory information regarding the prognostic importance of adipocytokines, hepatic and inflammatory biomarkers on the incidence of type 2 diabetes. The objective was to assess the prognostic relevance of adipocytokine and inflammatory markers (C-reactive protein – CRP; interleukin-1beta – IL-1β; interleukin-6– IL-6; tumour necrosis factor-α – TNF-α; leptin and adiponectin) and gamma-glutamyl transpeptidase (γGT) on the incidence of type 2 diabetes. Methods Prospective, population-based study including 3,842 non-diabetic participants (43.3% men, age range 35 to 75 years), followed for an average of 5.5 years (2003–2008). The endpoint was the occurrence of type 2 diabetes. Results 208 participants (5.4%, 66 women) developed type 2 diabetes during follow-up. On univariate analysis, participants who developed type 2 diabetes had significantly higher baseline levels of IL-6, CRP, leptin and γGT, and lower levels of adiponectin than participants who remained free of type 2 diabetes. After adjusting for a validated type 2 diabetes risk score, only the associations with adiponectin: Odds Ratio and (95% confidence interval): 0.97 (0.64–1.47), 0.84 (0.55–1.30) and 0.64 (0.40–1.03) for the second, third and forth gender-specific quartiles respectively, remained significant (P-value for trend = 0.05). Adding each marker to a validated type 2 diabetes risk score (including age, family history of type 2 diabetes, height, waist circumference, resting heart rate, presence of hypertension, HDL cholesterol, triglycerides, fasting glucose and serum uric acid) did not improve the area under the ROC or the net reclassification index; similar findings were obtained when the markers were combined, when the markers were used as continuous (log-transformed) variables or when gender-specific quartiles were used. Conclusion Decreased adiponectin levels are associated with an increased risk for incident type 2 diabetes, but they seem to add little information regarding the risk of developing type 2 diabetes to a validated risk score.

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Blockade of the renin-angiotensin system and renal tissue oxygenation as measured with BOLD-MRI in patients with type 2 diabetes

To assess whether blockade of the renin-angiotensin system (RAS), a recognized strategy to prevent the progression of diabetic nephropathy, affects renal tissue oxygenation in type 2 diabetes mellitus (T2DM) patients.

QTc interval and resting heart rate as long-term predictors of mortality in type 1 and type 2 diabetes mellitus: a 23-year follow-up

We evaluated the association of QT interval corrected for heart rate (QT(c)) and resting heart rate (rHR) with mortality (all-causes, cardiovascular, cardiac, and ischaemic heart disease) in subjects with type 1 and type 2 diabetes.

Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus.

Factors associated with the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study

BACKGROUND: Human immunodeficiency virus (HIV)-infected persons may be at increased risk for developing type 2 diabetes mellitus because of viral coinfection and adverse effects of treatment. METHODS: We studied associations of new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort Study, using Poisson regression. RESULTS: A total of 123 of 6513 persons experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU), resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval [CI], 3.7-5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was found for male subjects (IRR, 2.5; 95% CI, 1.5-4.2), older age (IRR for subjects >60 years old, 4.3; 95% CI, 2.3-8.2), black (IRR, 2.1; 95% CI, 1.1-4.0) and Asian (IRR, 4.9; 95% CI, 2.2-10.9) ethnicity, Centers for Disease Control and Prevention disease stage C (IRR, 1.6; 95% CI, 1.04-2.4), and obesity (IRR, 4.7; 95% CI, 3.1-7.0), but results for hepatitis C virus infection or active hepatitis B virus infection were inconclusive. Strong associations were found for current treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI, 1.11-4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors (IRR, 2.48; 95% CI, 1.42-4.31), and nucleoside reverse-transcriptase inhibitors plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR, 3.25; 95% CI, 1.59-6.67) but were not found for treatment with nucleoside reverse-transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors (IRR, 1.47; 95% CI, 0.77-2.82). CONCLUSIONS: In addition to traditional risk factors, current treatment with protease inhibitor- and nucleoside reverse-transcriptase inhibitor-containing regimens was associated with the risk of developing type 2 diabetes mellitus. Our study did not find a significant association between viral hepatitis infection and risk of incident diabetes.

Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.

Retinol-binding protein 4 is associated with components of the metabolic syndrome, but not with insulin resistance, in men with type 2 diabetes or coronary artery disease

AIMS/HYPOTHESIS: Retinol-binding protein 4 (RBP4) has recently been reported to be associated with insulin resistance and the metabolic syndrome. This study tested the hypothesis that RBP4 is a marker of insulin resistance and the metabolic syndrome in patients with type 2 diabetes or coronary artery disease (CAD) or in non-diabetic control subjects without CAD. METHODS: Serum RBP4 was measured in 365 men (126 with type 2 diabetes, 143 with CAD and 96 control subjects) and correlated with the homeostasis model assessment of insulin resistance index (HOMA-IR), components of the metabolic syndrome and lipoprotein metabolism. RBP4 was detected by ELISA and validated by quantitative Western blotting. RESULTS: RBP4 concentrations detected by ELISA were shown to be strongly associated with the results gained in quantitative Western blots. There were no associations of RBP4 with HOMA-IR or HbA(1c) in any of the groups studied. In patients with type 2 diabetes there were significant positive correlations of RBP4 with total cholesterol, LDL-cholesterol, VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity. In patients with CAD, there were significant associations of RBP4 with VLDL-cholesterol, plasma triacylglycerol and hepatic lipase activity, while non-diabetic control subjects without CAD showed positive correlations of RBP4 with VLDL-cholesterol and plasma triacylglycerol. CONCLUSIONS/INTERPRETATION: RBP4 does not seem to be a valuable marker for identification of the metabolic syndrome or insulin resistance in male patients with type 2 diabetes or CAD. Independent associations of RBP4 with pro-atherogenic lipoproteins and enzymes of lipoprotein metabolism indicate a possible role of RBP4 in lipid metabolism.