IL-15 that a regulator of TNF-α in patients with diabetes mellitus type 2

Diabetes mellitus type 2 (DM2), obesity, and the metabolic syndrome are considered that a low-grade chronic inflammatory condition. Although synthesis of different pro- and anti-inflammatory cytokines has been implicated in this process, this low-grade inflammatory condition is characterized especially by an increase in Tumor Necrosis Factor alpha (TNF-α), a cytokine that has been associated to the development of insulin resistance and muscle wasting in the diabetic patients. In consequence, mechanisms implicated in attenuating the deleterious effects of TNF-α are activated. One of these mechanisms may involve interleukin 15 (IL-15), which has proven effect on intermediate metabolisms, regulating blood glucose and lipid levels, and diminishing proteolysis in striated muscle. This suggests that the induction of endogenous IL-15 production by a simple event as physical activity may aid in decreasing or even inhibiting the negative effects of TNF-α in patient with DM2 or obesity, in which a low grade chronic inflammatory condition is present.     

Exercise training-induced enhancement in myocardial mechanics is lost after 2 weeks of detraining in rats

Exercise training is assumed to improve myocardial function; however, the role of detraining and its effect on myocardial parameters are still unclear. The aim of the present study was to evaluate the effect of detraining on ventricular remodeling and myocardial mechanical parameters after an 8 week (5 days/week, 60 min/day) swimming training period. Forty-three female Wistar rats were distributed into six groups: trained (T, n = 9), detrained 2 weeks (D2, n = 8), detrained 4 weeks (D4, n = 8) and their respective controls: untrained (U, n = 5), untrained 2 weeks (U2, n = 5) and untrained 4 weeks (U4, n = 5). Detrained rats underwent training and then remained sedentary (i.e., “detraining”) for 2 or 4 weeks. After training, the T group demonstrated increased physical capacity, left ventricular (LV) posterior wall thickness, and LV end-diastolic diameter, along with decreased heart rate, as evaluated by echocardiogram. In addition, the inotropism and lusitropism parameters studied on papillary muscles showed improvement in the T group (P < 0.05). However, after just 2 weeks of detraining, all parameters regressed back to values which were similar to those of the untrained groups. In conclusion, our results confirmed that exercise training is capable of inducing myocardial remodeling and improving contractile performance; however, these changes are completely lost after a short period of detraining.     

Diabetic ketoacidosis with a fatal issue: is it a MODY3 (maturity-onset diabetes of the young type 3)?

Ketoacidotic coma is one of the possible diabetes mellitus first symptoms. It results from complete or relative lack of insuline and is often associated with type 1 diabetes. The authors report a case of a 45-years old woman with inaugural diabetes of which atypical features have motivated the study of MODY gene (maturity-onset diabetes of the young). Gly574ser polymorphism in the HNF-1alpha gene was found, in homozygous state, and the question of the responsibility of this polymorphism in this diabete is asked.     

A flexible sequential learning deficit in patients with Parkinson’s disease: a 2 × 8 button-press task

A 2 × 8 button-press task is a sequential hand movement task in which subjects are required to press eight pairs of buttons as accurately and quickly as possible. The 2 × 8 task allows us to examine flexible sequential learning, more aptly called sequence-unselective learning. Sequence-unselective learning is observed after repeated experiences with the task, when subjects have shown good progress in learning, with new sequences as well as previously learned ones. Although cognitive inflexibility has been reported in patients with Parkinson’s disease (PD), there have been few studies investigating their flexibility in sequential learning. We examined PD patients’ ability for sequence-unselective learning through the use of a 2 × 8 button-press task. In the first session, PD patients and subjects from the control group performed a sequential 2 × 8 task until the learning criterion was fulfilled (Session 1). After 1 month, they participated in other sessions: one involving the learned sequence (Session 2) and another involving the new sequence (Session 3). We found that PD patients made more errors than the normal control subjects only when learning the new sequence (Session 3) (P < 0.01). In Session 3, control subjects reached the learning target with fewer errors than in the Session 1 (normal sequence-unselective learning), whereas the PD patients did not exhibit such an improvement. Our results revealed a sequence-unselective deficit in PD patients. The deficit may help to emphasize the cognitive and physical inflexibility of PD.     

Do patients’ beliefs about type 2 diabetes differ in accordance with complications: An investigation into diabetic foot ulceration and retinopathy

Background: Previous research has examined patients’ beliefs in diabetes and how these beliefs may affect patient outcomes. However, changes in symptoms and complications are a common feature of diabetes, and these can significantly alter the patient’s “disease experience.” However, no consideration has been given to how beliefs about diabetes vary according to the complications patients have. Purpose: The present study was designed to compare the beliefs of 22 patients with diabetic foot ulcers and 22 age- and gender-matched patients with diabetic retinopathy, and 22 age- and gender-matched controls with type 2 diabetes but without either complication. Methods: Beliefs about diabetes were assessed with the Revised Illness Perception Questionnaire (IPQ-R; Moss-Morris et al., 2002). Results: Patients with foot ulcers held a greater belief in personal control of diabetes, but perceived treatment control was lower than that of diabetic controls without serious complications (p < .05). Patients with foot ulcers also demonstrated less illness coherence than patients with retinopathy and diabetic controls (p < .01) and also perceived their diabetes to be more cyclical in nature (p < .01). Conclusion. Differences were found in diabetic patients’ beliefs according to their complications. Future interventions should consider how the complications associated with diabetes may affect patients’ beliefs and subsequent emotional and behavioral responses to the disease.     

Effect of an ‘implementation intention’ intervention on adherence to oral anti-diabetic medication in Brazilians with type 2 diabetes

ObjectiveTo evaluate the effects of an implementation intention intervention on adherence to an oral anti-diabetic medication regime, diabetes-related distress and on glycemic control in patients with type 2 diabetes mellitus.MethodsA randomized, parallel-group, single-center controlled trial was conducted among adults with type 2 diabetes being managed at the primary care level. The intervention group (IG, n = 45) received an ‘implementation intention’ intervention; the control group (CG, n = 45) received standard care. Primary outcomes were the taking of oral anti-diabetic medication, global adherence and level of glycated hemoglobin. The secondary outcome was diabetes-related distress. Data were gathered at baseline and after 15 weeks.ResultsThe IG showed improvements in adherence to an oral anti-diabetic medication regime (p < 0.0001), glycemic control (p < 0.0001) and diabetes-related distress (p < 0.0001) relative to the CG.ConclusionsThe implementation intention intervention enhanced adherence to an oral anti-diabetic medication regime, which had positive effects on blood glucose levels and diabetes-related distress.Practice implicationsAdherence to an oral anti-diabetic medication regime can decrease blood glucose levels and diabetes-related distress and thus reduce complications of type 2 diabetes.     

Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra^®, a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra^® at doses equivalent to their previous treatment. IgG levels achieved with Hizentra^® were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra^®-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra^® maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.     

The gene–treatment interaction of paraoxonase-1 gene polymorphism and statin therapy on insulin secretion in Japanese patients with type 2 diabetes: Fukuoka diabetes registry

Background

Although statins deteriorate glucose metabolism, their glucose-lowering effects have emerged in some situations. Here, we assessed whether these effects are a consequence of statins’ interaction with paraoxonase (PON)1 enzyme polymorphism.

Methods

Adult Japanese type 2 diabetes patients (n?=?3798) were enrolled in a cross-sectional study. We used Q192R polymorphism of the PON1 gene as a representative single-nucleotide polymorphism and focused on the effects of the wild-type Q allele, in an additive manner. For patients with and without statin therapy, the associations of this allele with fasting plasma glucose (FPG), HbA_1c, C-peptide, HOMA2-%β, and HOMA2-IR were investigated separately using a linear regression model, and were compared between groups by testing interactions. Sensitivity analyses were performed using propensity score to further control the imbalance of characteristics between groups.

Results

Among patients with statin therapy, there were linear associations of the number of Q alleles with decreased FPG and HbA_1c, and with increased serum C peptide and HOMA2-%β (all P?<?0.01 for trends), while such associations were not observed among those without statin therapy. These differences were statistically significant only for serum C peptide and HOMA2-%β (P?<?0.01 for interactions). These associations remained significant after multiple explanatory variable adjustment. Sensitivity analyses using propensity score showed broad consistency of these associations.

Conclusions

Patients with the Q allele of the PON1 Q192R polymorphism who were treated with statins exhibited improvement in glucose metabolism, especially in insulin secretion, suggesting the importance of genotyping PON1 Q192R to identify those who could benefit from statin therapy.

     

Exacerbation of poststroke dementia by type 2 diabetes is associated with synergistic increases of β-secretase activation and β-amyloid generation in rat brains

We examined the effect of type 2 diabetes on stroke-induced Alzheimer's disease-like pathological and behavioral changes in rats. Rats were treated for 2 months with high fat diet (HFD) followed by streptozotocin (STZ) injection to induce type 2 diabetes (HFD-STZ model). Middle cerebral artery occlusion (MCAO) was used to induce cerebral focal ischemia. Animals were divided into four groups: Sham-NPD, Sham-HFD-STZ, MCAO-NPD and MCAO-HFD-STZ. The results showed that HFD-STZ treatment induced obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia, hyperglycemia and insulin resistance, characteristics of type 2 diabetes. The performance of rats in the Morris water maze test was impaired in MCAO-NPD and Sham-HFD-STZ rats, indicating cognitive deficits. Hippocampal caspase-3⁺ and beta amyloid (Aβ⁺) cell numbers, as well as β-site amyloid precursor protein–cleaving enzyme (BACE1) levels and activity, increased in both groups. Moreover, HFD-STZ treatment exacerbated stroke-induced cognitive deficits, additively increased MCAO-induced activation of caspase-3, and increased levels of BACE1, C99 and Aβ. However, the level of insulin decreased in MCAO-HFD-STZ rats. These results suggested that type 2 diabetes deteriorated stroke-induced brain damage and cognitive impairment, which might be associated with increased Aβ generation and cytotoxicity. We concluded that type 2 diabetes exacerbated poststroke dementia possibly due to brain injury and synergistic generation of Aβ via activation of BACE1.     

Elevation of small,dense low density lipoprotein cholesterol—a possible antecedent of atherogenic lipoprotein phenotype in type 2 diabetes patients in Jos,North-Central Nigeria

Background

The global prevalence of type 2 diabetes is increasing. Dyslipidaemia is a known complication of diabetes mellitus manifesting frequently as cardiovascular diseases and stoke. Elevation of small, dense low density lipoprotein has been recognised as a component of the atherogenic lipoprotein phenotype associated with cardiovascular complications. We speculate that the elevation of this lipoprotein particle may be the antecedent of the atherogenic lipoprotein phenotype. This study therefore aims to determine the pattern of dyslipidaemia among diabetes mellitus patients in Jos, North-Central Nigeria.

Methods

One hundred and seventy-six patients with type 2 diabetes and 154 age-matched controls were studied. The patients with diabetes were regular clinic attenders and had stable glycaemic control. None were on lipid-lowering therapy. Anthropometric indices, blood pressure, and lipids (including total cholesterol, high density lipoprotein cholesterol, and triglyceride) were measured by chemical methods using the Hitachi 902 analyzer. Low density lipoprotein cholesterol was calculated using the Friedewald’s equation. Small, dense low density lipoprotein cholesterol, ?sdLDL-C was measured using the precipitation method by Hirano et al. Means of the different groups were compared using EPI Info and a P-value of <0.05 was accepted as significant difference.

Results

Total cholesterol, low density lipoprotein cholesterol, triglyceride and small, dense lipoprotein cholesterol were all significantly higher in diabetes patients than controls except high density lipoprotein cholesterol. The percentage of LDL-C as sdLDL-C among the diabetes versus control group was 45%?±?17.79 v 32.0%?±?15.93. Serum sdLDL-C concentration was determined to be 1.45?±?0.64 among diabetes patients and 0.8?±?0.54 among control subjects. 75% of diabetes patients had hypertension and were taking blood pressure lowering medications.

Conclusion

The classical atherogenic lipoprotein phenotype was not demonstrated among subjects with type 2 diabetes mellitus in this study, but the elevation of serum small dense low density lipoprotein cholesterol in patients with sustained hypertension suggests the establishment of atherogenic complications among our diabetes patients.

     

Serum leptin level measured 48 h after delivery is associated with development of postpartum depressive symptoms: a 3-month follow-up study

The aim of this study was to assess the possible relationship between leptin status and postpartum depressive symptoms using serum levels of leptin collected 24–48 h after delivery in a cohort Chinese sample. Women delivering a full-term, singleton, and live-born infant in the period from August 2013 to March 2014 were enrolled immediately postpartum. A blood sample was obtained 24–48 h after childbirth to test serum levels of leptin. Participation consisted of a visit in an obstetric unit at 3 months after delivery. The Edinburgh Postnatal Depression Scale (EPDS), completed at 3 months postpartum, was used to classify each woman’s depression symptom severity. Demographic, obstetric, behavioral risk, mental health, and psychosocial factors were considered. Multiple logistic regression analyses were used to identify risk factors most predictive of postpartum depressive symptoms. During the study period, 407 individuals were included and completed follow-up. At 3 months, according to EPDS score, 53 women (13.0 %) were considered as postpartum depressive symptoms. Serum leptin levels in women with PPD were significantly greater than those in women without depressive symptoms (36.5 [IQR, 25.5–50.4] vs. 14.5 [IQR, 9.4–22.4]?ng/ml, P?<?0.0001). Based on the ROC curve, the optimal cutoff value of serum leptin levels as an indicator for predicting of depressive symptoms was projected to be 24.3 ng/mL, which yielded a sensitivity of 88.7 % and a specificity of 73.4 %, with the area under the curve at 0.867 (95 % CI, 0.817–0.916). In multivariate analysis, there was an increased risk of depressive symptoms associated with leptin levels ≥24.3 ng/ml (OR 8.234; 95 % CI, 3.572–15.876; P?<?0.0001) after adjusting for possible confounders. Elevated serum leptin levels at delivery could eventually serve as a biological marker for the prediction of depressive symptoms. These associations were independent of other possible variables.     

Treatment of acute coronary syndromes in patients with type 2 diabetes mellitus with β-adrenoblockers and angiotensin-converting enzyme inhibitors: cardiohemodynamic effects and impact for prognosis

Long-term oral treatment of patients with acute coronary syndromes and type 2 diabetes mellitus with -adrenoblockers and angiotensin-converting enzyme inhibitors is associated with positive, though ambiguous changes in the left-ventricular structure and function. These changes should be the reason for choosing optimal therapy ensuring better prognosis in this patient population.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 9, pp. 341–344, September, 2004     

Quality of Life in Women with Localised Breast Cancer or Malignant Melanoma 2 Years After Initial Treatment: a Comparison

Background

Two thirds of female breast cancer patients and more than 80 % of malignant melanoma patients are diagnosed with localised disease and good prognosis with a 5-year relative survival of more than 90 % in Germany.

Purpose

This study was conducted to present quality of life (QoL) data from a German population-based cohort of female breast cancer and melanoma patients without recurrence for approximately 2 years after initial diagnosis.

Methods

In 2003–2004, patients with localised breast cancer and melanoma were recruited from the Munich Cancer Registry (Upper Bavaria, Germany) to answer QoL questionnaires. Differences between breast cancer and melanoma patients were investigated with regard to age and aspects of communication with their medical caregivers.

Results

One thousand three hundred and four breast cancer and 348 melanoma patients were included. Breast cancer patients were about 7 years older and had significantly lower QoL and higher symptom scores than melanoma patients. Communication needs were generally similar in both groups; however, breast cancer patients experienced more empathy from their medical caregivers. In breast cancer patients, communication was an independent factor for all QoL functioning scores.

Conclusions

Even when faced with a similarly good prognosis, breast cancer patients have a worse QoL than melanoma patients 2 years after diagnosis. An explanation may be more distinctive surgery and systemic therapy, older patients with comorbidities and misunderstood risk communication in breast cancer patients that may stoke anxiety and fears. Further reasons could be unceasing public discussion about breast cancer and its instrumentalisation for political purposes.     

<Emphasis Type="Italic">Bgl</Emphasis>II gene polymorphism of the α2β1 integrin gene is a risk factor for diabetic retinopathy in Caucasians with type 2 diabetes

Platelets are thought to be involved in the pathogenesis of diabetic retinopathy. The BglII gene polymorphism of the 21 integrin, which is a platelet collagen receptor, has been suggested as a genetic risk factor for diabetic retinopathy in Japanese subjects. The aim of this study was to look for a relationship between the BglII gene polymorphism of the 21 integrin gene and the development of diabetic retinopathy in Caucasians with type 2 diabetes. Subjects with type 2 diabetes and diabetic retinopathy (n=163) were compared with diabetic subjects without diabetic retinopathy (n=95). A significantly higher frequency of the BglII (+/+) genotype of the gene polymorphism of the 21 integrin gene was found in patients with diabetic retinopathy compared with patients without diabetic retinopathy (19.6% vs 7.4%; P=0.008). The present study demonstrates that the BglII (+/+) genotype of the gene polymorphism of the 21 integrin gene is an independent risk factor (odds ratio: 2.4, 95% confidence interval 1.0–6.0; P<0.05) for diabetic retinopathy in Caucasians with type 2 diabetes.