Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs.

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

Distinct trajectories of HbA1c in newly diagnosed Type 2 diabetes from the DPV registry using a longitudinal group-based modelling approach.

AIM: To identify groups of heterogeneous HbA1c trajectories over time in newly diagnosed Type 2 diabetes. METHODS: The study comprised 6355 adults with newly diagnosed Type 2 diabetes (55% men, median age 62 years, baseline BMI 31 kg/m2 ) from the Diabetes Patienten Verlaufsdokumentation (DPV) prospective multicentre diabetes registry (Germany, Austria). Individuals were assessed during the first 5 years after diabetes diagnosis if they had ≥ 3 aggregated HbA1c measurements during follow-up. Latent class growth modelling was used to determine distinct subgroups that followed similar longitudinal HbA1c patterns (SAS: Proc Traj). Multinomial logistic regression models were used to investigate which variables were associated with the respective HbA1c trajectory groups. RESULTS: Four distinct longitudinal HbA1c trajectory (glycaemic control) groups were found. The largest group (56% of participants) maintained stable good glycaemic control (HbA1c 42-45 mmol/mol). Twenty-six percent maintained stable moderate glycaemic control (HbA1c 57-62 mmol/mol). A third group (12%) initially showed severe hyperglycaemia (HbA1c 97 mmol/mol) but reached good glycaemic control within 1 year. The smallest group (6%) showed stable poor glycaemic control (HbA1c 79-88 mmol/mol). Younger age at diabetes diagnosis, male sex, and higher BMI were associated with the stable moderate or poor glycaemic control groups. Insulin therapy was strongly associated with the highly improved glycaemic control group. CONCLUSIONS: Four subgroups with distinct HbA1c trajectories were determined in newly diagnosed Type 2 diabetes using a group-based modelling approach. Approximately one-third of people with newly diagnosed Type 2 diabetes need either better medication adherence or earlier intensification of glucose-lowering therapy.

Inverse association of insulin antibody levels with insulin sensitivity in adults with Type 1 diabetes.

AIMS: Insulin resistance may contribute to the pathogenesis of autoimmune-mediated diabetes. Antibodies against ß-cell-associated molecules, comprising islet cell antigen (ICA), glutamic acid decarboxylase (GAD) and insulin, characterize the autoimmune process. Because the link between insulin resistance and autoimmunity might be relevant for disease progression and treatment, we hypothesized that insulin resistance associates positively with ß-cell-directed antibodies in newly diagnosed Type 1 diabetes. METHODS: Within the German Diabetes Study, an observational study including adults with newly diagnosed diabetes, 142 adults [84 men, 58 women; age 33.1 (26.4, 41.9) years; diabetes duration 6.3 (4.2, 9.1) months] positive for at least one antibody against ICA, GAD or insulin underwent hyperinsulinaemic-euglycaemic clamp tests to assess insulin sensitivity (M-value) in a cross-sectional setting. RESULTS: Insulin-directed antibodies were inversely correlated with M-values (ß = -0.039). Albeit not strong, the association persisted after adjustment for age, sex and BMI, and even after further adjustment for confounders reflecting exposure to exogenous insulin and residual ß-cell secretory capacity. Correlation network-based analyses revealed a complex interaction between levels of fasting insulin and of insulin antibodies with respect to their relationship with the M-value. GAD- or ICA-directed antibodies did not correlate with insulin sensitivity. CONCLUSIONS: In adults with recent-onset Type 1 diabetes expressing at least one ß-cell-directed antibody, insulin sensitivity is inversely related to insulin antibody titres, but not to other autoantibodies. Our finding may allow for the identification of insulin resistance in adults with high levels of insulin antibodies.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes.

AIMS: To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and ß-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. METHODS: Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic ß-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. RESULTS: Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% (P = 0.035). CONCLUSIONS: Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093).

Do dogs sense hypoglycaemia?

AIMS: To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it. METHODS: Electronic databases were searched for all types of articles reporting on untrained or trained 'diabetes alert' dogs. Articles published up until December 2014 in the English or German language were included. RESULTS: Several case reports and observational studies provide evidence that animals can perform at a level above that attributable to chance, and may reliably detect low diurnal as well as nocturnal hypoglycaemic episodes. Behavioural changes in untrained dogs were reported during 38-100% of hypoglycaemic events experienced by their owners. The sensitivity and specificity of the performance of trained diabetes alert dogs sensing hypoglycaemia ranged from 22 to 100% and 71 to 90%, respectively. Additionally, 75-81% of patients with diabetes who owned a trained dog reported a subsequent improvement in their quality of life. Nevertheless, the available data are limited and heterogeneous because they rely on low patient numbers and survey-based studies prone to recall bias. CONCLUSION: Further research is needed to confirm the preliminary data on the reliability and mechanism underlying the dogs' abilities to detect hypoglycaemia, and its impact on patient outcomes.

Simplified analysis of acetaminophen glucuronide for quantifying gluconeogenesis and glycogenolysis using deuterated water.

Measurement of acetaminophen glucuronide (AG) (2)H enrichment from deuterated water ((2)H2O) by (2)H nuclear magnetic resonance (NMR) analysis of its monoacetone glucose (MAG) derivative provides estimation of gluconeogenic and glycogenolytic contributions to endogenous glucose production (EGP). However, AG derivatization to MAG is laborious and unsuitable for high-throughput studies. An alternative derivative, 5-O-acetyl monoacetone glucuronolactone (MAGLA), was tested. Eleven healthy subjects ingested (2)H2O to 0.5% body water enrichment and 500 mg of acetaminophen. Plasma glucose and urinary glucuronide positional (2)H enrichments were measured by (2)H NMR spectroscopy of MAG and MAGLA, respectively. A Bland-Altman analysis indicated agreement at the 95% confidence level between glucose and glucuronide estimates.

Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy.

AIMS: To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy. METHODS: The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation. Omentin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum omentin level was inversely associated with polyneuropathy after adjustment for age, sex, height, waist circumference, hypertension, total cholesterol, smoking, alcohol intake and physical activity [odds ratio 0.45 (95% CI 0.21-0.98); P = 0.043]. Although omentin was positively correlated with adiponectin (r = 0.55, P < 0.0001) and inversely with tumour necrosis factor-α (r = -0.30, P = 0.019), additional adjustment for adiponectin and tumour necrosis factor-α had little impact on the association. CONCLUSIONS: Serum levels of omentin are reduced in people with Type 2 diabetes and diabetic sensorimotor polyneuropathy, independently of established risk factors of polyneuropathy. This association is only partially explained by biomarkers of subclinical inflammation.

Imeglimin increases glucose-dependent insulin secretion and improves ß-cell function in patients with type 2 diabetes.

AIMS: To assess the glucose-stimulated insulin secretion effect of imeglimin in patients with type 2 diabetes. METHODS: We conducted a double-blind, randomized, placebo-controlled study in 33 patients with type 2 diabetes [glycated haemoglobin 6.8 ± 0.1% (51 mmol/mol)], who were drug-naïve or withdrawn from their previous metformin monotherapy for 2 weeks and received imeglimin 1500 mg twice daily or placebo for 1 week. Glucose-stimulated insulin secretion was assessed using a hyperglycaemic clamp. The primary endpoint was insulin secretion as defined by total insulin response [incremental area under the curve (iAUC)0-45 min ] and insulin secretion rate (ISR) calculated from C-peptide deconvolution. ß-cell glucose sensitivity at steady state (second phase: 25-45 min), hepatic insulin extraction and insulin clearance were also calculated. RESULTS: Imeglimin treatment for 7 days raised the insulin secretory response to glucose by +112% (iAUC0-45 , p = 0.035), first-phase ISR by +110% (p = 0.034) and second-phase ISR by +29% (p = 0.031). Imeglimin improved ß-cell glucose sensitivity by +36% (p = 0.034) and tended to decrease hepatic insulin extraction (-13%; p = 0.056). Imeglimin did not affect glucagon secretion. CONCLUSIONS: In patients with type 2 diabetes, imeglimin improves ß-cell function, which may contribute to the glucose-lowering effect observed with imeglimin in clinical trials.

[Prevention of Type 2 Diabetes: Evidence-Based Patient Information--A Randomised Controlled Trial]. / Effekt einer evidenzbasierten Patienteninformation zur Prävention von Typ 2-Diabetes.

The aim of this study was to compare the effect of our newly developed online evidence-based patient information (EBPI) vs. standard patient information about subthreshold elevated blood glucose levels and primary prevention of diabetes on informed patient decision-making. EBPI significantly improved knowledge about elevated glucose levels, but also increased decisional conflict and critical attitudes to screening and treatment options. The intention to undergo metabolic screening decreased as a result.

Fasting and meal-stimulated residual beta cell function is positively associated with serum concentrations of proinflammatory cytokines and negatively associated with anti-inflammatory and regulatory cytokines in patients with longer term type 1 diabetes.

AIMS/HYPOTHESIS: Cytokines may promote or inhibit disease progression in type 1 diabetes. We investigated whether systemic proinflammatory, anti-inflammatory and regulatory cytokines associated differently with fasting and meal-stimulated beta cell function in patients with longer term type 1 diabetes. METHODS: The beta cell function of 118 patients with type 1 diabetes of duration of 0.75-4.97 years was tested using a standardised liquid mixed meal test (MMT). Serum samples obtained at -5 to 120 min were analysed by multiplex bead-based technology for proinflammatory (IL-6, TNF-α), anti-inflammatory (IL-1 receptor antagonist [IL-1RA]) and regulatory (IL-10, TGF-ß1-3) cytokines, and by standard procedures for C-peptide. Differences in beta cell function between patient groups were assessed using stepwise multiple regression analysis adjusting for sex, age, duration of diabetes, BMI, HbA1c and fasting blood glucose. RESULTS: High fasting systemic concentrations of the proinflammatory cytokines IL-6 and TNF-α were associated with increased fasting and stimulated C-peptide concentrations even after adjustment for confounders (p < 0.03). Interestingly, increased concentrations of anti-inflammatory/regulatory IL-1RA, IL-10, TGF-ß1 and TGF-ß2 were associated with lower fasting and stimulated C-peptide levels (p < 0.04), losing significance on adjustment for anthropometric variables. During the MMT, circulating concentrations of IL-6 and TNF-α increased (p < 0.001) while those of IL-10 and TGF-ß1 decreased (p < 0.02) and IL-1RA and TGF-ß2 remained unchanged. CONCLUSIONS/INTERPRETATION: The association between better preserved beta cell function in longer term type 1 diabetes and increased systemic proinflammatory cytokines and decreased anti-inflammatory and regulatory cytokines is suggestive of ongoing inflammatory disease activity that might be perpetuated by the remaining beta cells. These findings should be considered when designing immune intervention studies aimed at patients with longer term type 1 diabetes and residual beta cell function.

Effects of pioglitazone versus glimepiride exposure on hepatocellular fat content in type 2 diabetes.

AIMS: Thiazoledinediones decrease blood glucose by their insulin-sensitizing properties. Here, we examined whether pioglitazone plus nateglinide (PIO) interferes with hepatocellular lipid (HCL) content and/or improves insulin sensitivity in well-controlled non-obese patients with type 2 diabetes mellitus (T2DM). METHODS: Sixteen patients [body mass index (BMI): 28 ± 1 kg/m(2) ; HbA1c: 7.1 ± 0.6%] were studied in a randomized, double-blind, 12-week parallel group trial, whereas matched healthy humans [non-diabetic control subjects (CON), BMI: 26 ± 1 kg/m(2)] were studied once. Treatment with pioglitazone (30 mg/day) plus nateglinide (PIO arm) to control for glimepiride-induced insulin secretion was compared to treatment with glimepiride (2 mg/day) plus placebo (GLI arm). Multinuclei magnetic resonance spectroscopy (MRS) was combined with pancreatic normoglycaemic-two-step-insulin clamps and stable isotopes to assess glucose turnover, glucose transport/phosphorylation, HCL and intramyocellular lipid (IMCL) contents, non-esterified fatty acids (NEFA) and adipokines. RESULTS: At baseline, HCL was approximately 5.6-fold higher in T2DM (p < 0.05 vs. CON). This was paralleled by approximately doubled leptin : adiponectin ratios (p < 0.05). HCL decreased by approximately 39% (p < 0.05) after PIO and only tended to decrease after GLI (p = 0.12). Treatment with PIO did not affect leptin : adiponectin ratios, but slightly improved (p < 0.05) insulin-mediated NEFA suppression, which related to lower HCL. PIO further prevented the insulin-induced increase in IMCL content of soleus and tibialis anterior muscles. Peripheral and hepatic insulin sensitivity, glucose transport and glycaemic control did not change in both groups. CONCLUSION: Short-term, low-dose thiazolidendione treatment improves insulin sensitivity of lipolysis and HCL, without affecting muscle and liver insulin sensitivity. It appears that metabolic PIO action in T2DM is primarily mediated via a decline in HCL associated with greater sensitivity of lipolysis to insulin.

Spontaneous obesity-linked type 2 diabetes in the absence of islet amyloid in a cynomolgus monkey infected with bovine spongiform encephalopathy.

A 9-year-old cynomolgus monkey (Macaca fascicularis) infected orally with bovine spongiform encephalopathy (BSE) was presented for necropsy following euthanasia 4 years post infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of type 2 diabetes (T2D). In contrast, macaque R984 developed rapid weight loss, hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet amyloid deposits were present. Immunostaining of pancreas sections for insulin and glucagon confirmed the loss of endocrine cells. In addition, prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal prion spread from the gut during the preclinical phase of BSE infection. Plasma glucose and insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet amyloid deposits could have been due to early prion spread from the periphery to the endocrine system or could have occurred spontaneously.

Exercise in type 2 diabetes: to resist or to endure?

There is now evidence that a single bout of endurance (aerobic) or resistance exercise reduces 24 h post-exercise subcutaneous glucose profiles to the same extent in insulin-resistant humans with or without type 2 diabetes. However, it remains to be determined which group would benefit most from specific exercise protocols, particularly with regard to long-term glycaemic control. Acute aerobic exercise first accelerates translocation of myocellular glucose transporters via AMP-activated protein kinase, calcium release and mitogen-activated protein kinase, but also improves insulin-dependent glucose transport/phosphorylation via distal components of insulin signalling (phosphoinositide-dependent kinase 1, TBC1 domain family, members 1 and 4, Rac1, protein kinase C). Post-exercise effects involve peroxisome-proliferator activated receptor-γ coactivator 1α and lead to ATP synthesis, which may be modulated by variants in genes such as NDUFB6. While mechanisms of acute resistance-type exercise are less clear, chronic resistance training activates the mammalian target of rapamycin/serine kinase 6 pathway, ultimately increasing protein synthesis and muscle mass. Over the long term, adherence to rather than differences in metabolic variables between specific modes of regular exercise might ultimately determine their efficacy. Taken together, studies are now needed to address the variability of individual responses to long-term resistance and endurance training in real life.

Precision and accuracy of blood glucose measurements using three different instruments.

AIMS: Assessment of insulin sensitivity by dynamic metabolic tests such as the hyperinsulinemic euglycemic clamp critically relies on the reproducible and fast measurement of blood glucose concentrations. Although various instruments have been developed over the last decades, little is known as to the accuracy and comparability. We therefore compared the best new instrument with the former gold standard instruments to measure glucose concentrations in metabolic tests. METHODS: Fasting blood samples of 15 diabetic and 10 healthy subjects were collected into sodium-fluoride tubes, spiked with glucose (0, 2.8, 6.9 and 11.1 mmol/l) and measured either as whole blood (range 3.3-26.3 mmol/l) or following centrifugation as plasma (range 3.9-32.0 mmol/l). Plasma samples were analyzed in the YSI-2300 STAT plus (YSI), EKF Biosen C-Line (EKF) and the reference method, Beckman Glucose analyzer-II (BMG), whole blood samples in EKF instruments with YSI as reference method. RESULTS: The average deviation of the EKF from the reference, BMG, was 3.0 ± 3.5% without any concentration-dependent variability. Glucose measurements by YSI were in good agreement with that by BMG (plasma) and EKF (plasma and whole blood) up to concentrations of 13.13 mmol/l (0.5 ± 3.7%), but deviation increased to -6.2 ± 3.8% at higher concentrations. Precision (n = 6) was ±2.2% (YSI), ±3.9% (EKF) and ±5.2% (BMG). CONCLUSIONS: The EKF instrument is comparable regarding accuracy and precision to the reference method BMG and can be used in metabolic tests, while the YSI showed a systematic shift at higher glucose concentrations. Based on these results we decided to replace BMG with EKF instrument in metabolic tests.

Non-esterified fatty acid dynamics during oral glucose tolerance test in women with former gestational diabetes.

AIMS: Women with former gestational diabetes are at increased risk of Type 2 diabetes, which likely relates to hyperlipidaemia and ectopic lipid storage, mainly in the liver. Here, we examined the response of non-esterified fatty acid dynamics to oral glucose loading (oral glucose tolerance test). METHODS: We studied women with former gestational diabetes with normal glucose tolerance (n = 60) or impaired glucose metabolism (n = 12) and compared them with healthy women after normal pregnancy (control subjects, n = 15). During a 3-h oral glucose tolerance test, glucose, insulin and non-esterified fatty acid were frequently measured to compute the area under the non-esterified fatty acid curve and parameters of ß-cell function and insulin sensitivity. Through mathematical modelling, we assessed insulin sensitivity of lipolysis inhibition and the fractional non-esterified fatty acid turnover rate. We also measured some serum liver enzymes. RESULTS: Women with former gestational diabetes were slightly older and had greater body mass than control subjects. Subjects with impaired glucose metabolism had lower oral glucose insulin sensitivity, but higher fasting insulin and area under the non-esterified fatty acid curve, which inversely related to oral glucose insulin sensitivity and independently determined mean glycaemia. Model-derived non-esterified fatty acid parameters were lower in subjects with impaired glucose metabolism than in control subjects, particularly sensitivity of non-esterified fatty acid inhibition to insulin (2.50 ± 0.52 vs. 1.06 ± 0.20 · 10(-2) ml/µU). Also, subjects with impaired glucose metabolism had higher liver transaminases. However, all non-esterified fatty acid parameters showed only modest inverse correlation with liver transaminases. CONCLUSIONS: Despite greater insulinaemia, circulating non-esterified fatty acids are higher in women with former gestational diabetes than in control subjects, which likely results from reduced sensitivity of lipolysis inhibition to insulin. This parameter may serve as indicator of an early metabolic derangement in this population at risk for diabetes.

Blood glucose testing and primary prevention of Type 2 diabetes-evaluation of the effect of evidence-based patient information: a randomized controlled trial.

AIMS: To compare the effect of our newly developed online evidence-based patient information vs. standard patient information about sub-threshold elevated blood glucose levels and primary prevention of diabetes on informed patient decision making. METHODS: We invited visitors to the cooperating health insurance company, Techniker Krankenkasse, and the German Diabetes Center websites to take part in a web-based randomized controlled trial. The population after randomization comprised 1120 individuals aged between 40 and 70 years without known diabetes, of whom 558 individuals were randomly assigned to the intervention group receiving evidence-based patient information, and 562 individuals were randomly assigned to the control group receiving standard information from the Internet. The primary endpoint was acquired knowledge of elevated blood glucose level issues and the secondary outcomes were attitude to metabolic testing, intention to undergo metabolic testing, decisional conflict and satisfaction with the information. RESULTS: Overall, knowledge of elevated glucose level issues and the intention to undergo metabolic testing were high in both groups. Participants who had received evidence-based patient information, however, had significantly higher knowledge scores. The secondary outcomes in the evidence-based patient information subgroup that completed the 2-week follow-up period yielded significantly lower intention to undergo metabolic testing, significantly more critical attitude towards metabolic testing and significantly higher decisional conflict than the control subgroup (n=466). Satisfaction with the information was not significantly different between both groups. CONCLUSIONS: Evidence-based patient information significantly increased knowledge about elevated glucose levels, but also increased decisional conflict and critical attitude to screening and treatment options. The intention to undergo metabolic screening decreased. Future studies are warranted to assess uptake of metabolic testing and satisfaction with this decision in a broader population of patients with unknown diabetes.

Increased serum concentrations of adhesion molecules but not of chemokines in patients with Type 2 diabetes compared with patients with Type 1 diabetes and latent autoimmune diabetes in adult age: action LADA 5.

AIMS: Systemic concentrations of adhesion molecules and chemokines are associated with increased risk of cardiovascular complications. We compared these factors between patients with Type 2 diabetes vs. Type 1 diabetes or latent autoimmune diabetes in adults. METHODS: Serum concentrations of adhesion molecules sE-selectin, sICAM-1 and sVCAM-1, and chemokines CCL2, CCL3 and CCL4 were measured in 61 patients with latent autoimmune diabetes in adults, 90 with Type 1 diabetes, 465 with Type 2 diabetes and in 41 control subjects, using multiple regression models to adjust for possible confounders. RESULTS: Patients with Type 2 diabetes exhibited greater concentrations of adhesion molecules (P < 0.02) than those with Type 1 diabetes, latent autoimmune diabetes in adults and control subjects. These differences persisted upon adjustments for age, sex, BMI, blood pressure and diabetes duration (P < 0.04). Higher BMI positively correlated with concentrations of adhesion molecules in all subjects (P < 0.0001). Concentrations of sE-selectin positively related to diastolic (ß = 0.31) and systolic (ß = 0.28) blood pressure in the adjusted model (P < 0.04). Concentrations of the chemokines, CCL2 and CCL4, did not differ between groups, while CCL3 was higher in patients with latent autoimmune diabetes in adults and Type 1 diabetes than in those with Type 2 diabetes and control subjects (P < 0.05). CONCLUSIONS: Systemic concentrations of adhesion molecules, but not chemokines, relate to cardiovascular risk factors, but remain higher after adjustments in Type 2 diabetes, suggesting a diabetes-type specific effect without difference between latent autoimmune diabetes in adults and Type 1 diabetes, despite their dissimilar phenotype.