Daytime Glibenclamide and Bedtime NPH Insulin Compared to Intensive Insulin Treatment in Secondary Sulphonylurea Failure: a 1-Year Follow-up

The aim of this study was to compare the metabolic effects of a combination of daytime glibenclamide and evening NPH insulin with intensive insulin treatment (rapid acting insulin before meals and NPH insulin at bedtime) in patients exhibiting secondary failure to sulphonylurea treatment. Thirty-nine mildly obese NIDDM patients (BMI 25.6 ± 0.5) were randomized after 6 weeks of intensive insulin treatment to either a combination treatment (CT, n = 20) or continued intensive insulin treatment (IT, n = 19). There were no differences between the two groups in age, diabetes duration, BMI, HbA_1c, or basal and glucagon stimulated C-peptide. The patients were followed for 1 year and the findings were analysed on an intent to treat basis. Two patients in the CT group were excluded after 2 and 6 months, respectively, due to unacceptably high postprandial glucose values. There was a significant difference in HbA_1c between the CT and IT groups at 6 months (8.2 ± 0.2, n = 19, vs 6.8 ± 0.4%, n = 19, p < 0.001)), but not at 12 months (7.8 ± 0.3, n = 18, vs 7.5 ± 0.4%, n = 19). After the initial intensive insulin treatment, BMI was constant in the CT group but increased significantly at 6 and 12 months in the IT group. We conclude that both treatments are associated with a marked and long-term improvement of glycaemic control. The intensive insulin treatment leads to a more pronounced weight increase which in the long run might have negative effect on overall metabolic control. Therefore, the combination treatment together with intensified education and dietary advice should be regarded as the initial treatment of choice for oral agent failure in moderately obese NIDDM patients.     

Recurrent Hypoglycaemia Associated with First and Second Trimester Insulin Sensitivity in a Patient with Insulin-dependent Diabetes

A 35-year-old insulin-dependent diabetic woman presented at 8 weeks gestation with multiple severe hypoglycaemic episodes occurring during the day and night without warning. Her pre-pregnancy insulin dosage of 45 units daily was progressively reduced by 73 % to 12 units daily by week 17 because of multiple hypoglycaemic episodes. Investigation showed no pathological cause for the hypoglycaemia. Insulin dosage increased to 16 units daily by week 19 and then increased sharply to 60 units daily at 23 weeks and finally to 72 units at week 37. Following delivery her insulin dosage returned to pre-pregnancy values. Insulin-dependent diabetic women may rarely develop exaggerated insulin sensitivity in the first trimester of pregnancy resulting in severe hypoglycaemia, but spontaneous improvement occurs with increasing insulin resistance in the second and third trimesters.     

Identification of predictors of the ovarian response to clomiphene citrate in infertile women with polycystic ovary syndrome: a prospective cohort study

ObjectiveTo identify predictors of the ovarian response to clomiphene citrate (CC) in infertile patients with polycystic ovary syndrome (PCOS).MethodsWe performed a prospective cohort study of infertile patients with PCOS. The participants underwent assessments of their physical, endocrine, and metabolic characteristics, and treatment with CC at an initial dose of 50 mg/day and a maximum of 100 mg/day between days 3 and 7 of their menstrual cycles. Participants who ovulated were identified as responders and those who did not as non-responders.ResultsOf the 72 participants, 48 (66.7%) were identified as responders and 24 as non-responders. Sex hormone-binding globulin (SHBG) (odds ratio 1.022, 95% confidence interval: 1.000–1.045) was found to be associated with the ovarian response to CC using logistic multivariate regression analysis. Receiver operating characteristic analysis also showed that SHBG was a significant predictor of the response to CC (area under the curve 0.799).ConclusionWe have shown that SHBG is the best prognostic indicator of an ovulatory response to CC. However, larger prospective studies, in which more variables are assessed, are required to confirm this finding and to identify appropriate cut-off values.     

山药多糖延缓秀丽隐杆线虫衰老的药效评价及作用机制研究

目的：基于秀丽隐杆线虫模型考察山药多糖的抗衰老药效并探究其作用机制。方法：基于秀丽隐杆线虫模型,利用寿命、咽泵频率、身体活动频率、脂褐素荧光、抗压性实验、活性氧荧光、抗氧化酶活性等指标考察山药多糖的抗衰老药理活性;通过转录组数据分析,探究山药多糖的抗衰老药效机制。结果：山药多糖可以显著延长线虫的寿命,缓解衰老过程中咽泵频率以及身体活动频率的下降,降低衰老过程中脂褐素及活性氧积累并提高线虫的抗压能力和抗氧化活性。转录组学京都基因和基因组百科全书(KEGG)通路分析发现,内分泌系统、细胞的生长和凋亡通路发生了显著的变化。山药多糖调控了30个与衰老相关的基因表达,且差异基因主要显著富集在自噬、哺乳动物雷帕霉素靶蛋白(mTOR)及胰岛素信号通路。结论：山药多糖具有抗衰老药理活性,转录组学数据揭示这种抗衰老作用可能与自噬、mTOR及胰岛素信号通路有关。     

Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels

To better characterize the role of the lipoprotein lipase (LPL) gene in the determination of triglyceride levels in healthy subjects, a study was performed in 193 nuclear families (384 parents, means age = 42.0 ± 5.2 years; 399 offspring, mean age = 14.6 ± 4.3 years) volunteering to have a free health checkup examination. The pattern of familial resemblance was compatible with a zero correlation between spouses, a weak father-offspring correlation (0.099 ± 0.054; P < 0.07), and significant mother-offspring (0.235 ± 0.053; P < 10⁻⁴) and sib-sib (0.294 ± 0.064; P < 10⁻⁴) correlations. Associations of triglyceride levels with the LPL HindIII and PvuII polymorphisms were investigated by a familial measured genotype analysis, specifying sex- and age-dependent polymorphism effects. The effects associated with both polymorphisms were significant only in fathers, the H+ and P+ alleles being associated with raised triglyceride levels. The HindIII and PvuII polymorphisms explained 3.5% and 3%, respectively, of the variability of triglycerides in fathers. The relationship was weakened after prior adjustment on body mass index, but remained significant for PvuII. Because of the lack of effect in mothers and offspring, the polymorphisms did not contribute to the covariance of triglyceride levels in relatives. In conclusion, this family study showed a weak relationship of the HindIII and PvuII polymorphisms to plasma triglyceride levels in young healthy male subjects. The effects detectable only in fathers suggest a possible modulation of the LPL expression by hormonal or lifestyle factors. © 1996 Wiley-Liss, Inc.     

Ethnic differences in self-reported functional status in the rural south: The johnston county osteoarthritis project

Objective. We examined ethnic differences in self-reported functional status in a rural, population-based sample in North Carolina. Methods. Data from 1,197 African-American and Caucasian participants, aged 45 and older, in the Johnston County Osteoarthritis Project were analyzed using multiple logistic regression to examine ethnic differences in difficulty performing tasks of the Health Assessment Questionnaire (HAQ) and in risk factor profiles associated with difficulty. Results. Forty-three percent reported difficulty in one or more HAQ tasks. African-Americans were more likely than Caucasians to report difficulty performing 3 tasks (P < 0.04); these differences were minimal after adjustment for confounders. For some tasks, risk factor profiles included body mass index in African-Americans only, and age and female gender more often in Caucasians. Low educational attainment was part of the risk factor profile for walking in African-Americans. Conclusions. Differences in proportions of African-Americans and Caucasians reporting difficulty in performance of HAQ tasks were minimal, but risk factor profiles for difficulty appeared to vary by ethnicity.     

AT1 receptor downregulation: A mechanism for improving glucose homeostasis

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-Ⅱ enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a m...     

Atherogenic Indices Can Predict Atherosclerosis in Patients with Sarcoidosis

Background:Sarcoidosis, a multisystemic disease of unknown etiology, is characterized by non-caseating granulomatous inflammation. This study aimed to investigate the efficiency of atherogenic indices and ultrasonographic evaluation of carotid artery on predicting atherosclerosis in patients with sarcoidosis.Methods:The study included 44 subjects followed with diagnosis of sarcoidosis and 53 age and gender matched healthy subjects as controls. Laboratory findings, pulmonary function tests and carotid artery ultrasonography of all participants were evaluated.Results:Of the participants with sarcoidosis 70.5% was female and the mean age was 35.36±7.18 years, while 64.2% of the control group were female and the mean age was 33.58±8.13 years (P=0.511 and P=0.191, respectively). High-density-lipoprotein cholesterol level in the sarcoidosis group was significantly lower than that of the control group (P=0.017), while other cholesterol levels were higher than those of the controls (P<0.05). Intima-media thickness (IMT) and peak systolic velocity (PSV) of carotid artery were higher in patients with sarcoidosis (P<0.001 and P=0.009, respectively). Atherogenic indices (Atherogenic Index (AI), Atherogenic Coefficient (AC) and Cardiogenic Risk Ratio (CRR)) were higher in sarcoidosis group compared to the controls (P<0.001, for all parameters). IMT was positively correlated with PSV, AI, AC, and CRR. A positive correlation between PSV and atherogenic indices was also detected.Conclusions:Sarcoidosis may be a predisposing factor for atherosclerosis. Atherogenic indices, IMT of carotid artery and PSV might be considered predictors for atherosclerosis and cardiovascular diseases in asymptomatic sarcoidosis patients.     

Metabolic Regulation of Macrophage Activation

Macrophages, the central mediators of innate immune responses, being in the first-line of defense, they have to readily respond to pathogenic or tissue damage signals to initiate the inflammatory cascade. Such rapid responses require energy to support orchestrated production of pro-inflammatory mediators and activation of phagocytosis. Being a cell type that is present in diverse environments and conditions, macrophages have to adapt to different nutritional resources. Thus, macrophages have developed plasticity and are capable of utilizing energy at both normoxic and hypoxic conditions and in the presence of varying concentrations of glucose or other nutrients. Such adaptation is reflected on changes in signaling pathways that modulate responses, accounting for the different activation phenotypes observed. Macrophage metabolism has been tightly associated with distinct activation phenotypes within the range of M1-like and M2-like types. In the context of diseases, systemic changes also affect macrophage metabolism, as in diabetes and insulin resistance, which results in altered metabolism and distinct activation phenotypes in the adipose tissue or in the periphery. In the context of solid tumors, tumor-associated macrophages adapt in the hypoxic environment, which results in metabolic changes that are reflected on an activation phenotype that supports tumor growth. Coordination of environmental and pathogenic signals determines macrophage metabolism, which in turn shapes the type and magnitude of the response. Therefore, modulating macrophage metabolism provides a potential therapeutic approach for inflammatory diseases and cancer.     

Lipid accumulation product as useful predictors of stroke: A correlation analysis between lipid accumulation index/cerebral vascular hemodynamics indexes and risk factors of stroke in 3264 people undergoing physical examination in Xinjiang

Objective:To investigate the relationship between lipid accumulation index and cerebral hemodynamic integral value in 3264 people undergoing physical examination, so as to analyze the correlation between different lipid accumulation product index (LAP) levels and stroke risk factors.Methods:This cross-sectional study was conducted from January to December 2019 on 3264 adults at the age of 19 to 85 living in Urumqi, Xinjiang. The stroke related risk factors were evaluated by the questionnaire survey. The enrolled subjects were divided into Q1 group (n = 817), Q2 group (n = 815), Q3 group (n = 816) and Q4 group (n = 816) according to the quartile site at a low-to-high-score manner.Results:The proportion of males was significantly higher than that of females in Q2, Q3, and Q4 groups. The proportion of middle-aged people and the elderly in Q2, Q3, and Q4 groups was significantly higher than that of youths (P < .05). The proportion of patients with history of hypertension, hyperlipidemia, physical inactivity, and smoking, and the levels of systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, high-density cholesterol, low-density cholesterol, triglyceride, body mass index, waist circumference increased with the increase of LAP level in different groups (P < .05). On both sides of the cerebral hemodynamic integral value (CVHI) index, Vmean, Vmax, Vmin showed a decreasing trend whereas peripheral resistance, pulse velocity, Zcv, dynamic resistance, critical pressure level, difference between diastolic and critical pressure showed an increase trend with the increase of LAP level. The normal rate of CVHI in 4 groups (>75 points) was 97.4%, 89.7%, 87.0, and 80.8%, respectively, showing a decreasing trend. Logistic regression results showed that the higher the LAP, the higher the abnormal risk of CVHI.Conclusion:There is a positive correlation between LAP and CVHI, the higher the LAP, the higher the risk of CVHI abnormality, which should be concerned seriously.