Objective: Cigarette smoke and non-alcoholic fatty liver disease are risk factors for type 2 diabetes mellitus. However, the impact of smoking on diabetes risk among patients with non-alcoholic fatty liver disease remains unclear.
Methods: This study included 15,464 Japanese individuals. We defined non-alcoholic fatty liver disease based on abdominal ultrasound findings where excess alcohol intake and other liver diseases were excluded. We used Cox proportional regression analysis to identify risk factors for type 2 diabetes onset.
Results: During 16,446 person-years of follow-up, 223 of 2,714 non-alcoholic fatty liver disease patients developed type 2 diabetes; the cumulative incidence rate of type 2 diabetes was 13.6 per 1,000 person-years. The proportions of never, former, and current smokers (self-report) were 35.3%, 31.1%, and 33.6%, and 88.5%, 5.1%, and 6.4% in men and women, respectively. In a Cox regression model adjusted for sex, age, body mass index, waist circumference, alcohol intake, exercise, and alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, lipid profiles, and blood pressure values, relative to never smokers, current smokers with non-alcoholic fatty liver disease had an increased risk of type 2 diabetes (hazard ratio=2.05; 95% confidence interval: 1.43-2.94). In addition, former smoking affected the risk of type 2 diabetes; however, this effect was not statistically significant.
Conclusions: This longitudinal study showed that current smoking may act as a "second hit" and increase the risk of type 2 diabetes in patients with non-alcoholic fatty liver disease.
Introduction: Advanced glycation end products (AGEs) are frequently increased in the skin of subjects with type 2 diabetes mellitus (T2DM). This study aimed to examine the correlation of AGEs with cardiac autonomic neuropathy (CAN) in T2DM.
Methods: To this aim, 132 participants (88 men) with a mean age of 64.57 years and a median T2DM duration of 14.5 years were included. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm (both single and automated triplicate measurements). Diagnosis of CAN, sympathetic and parasympathetic nervous system impairment was based on the four standardised cardiovascular reflex tests (CARTs).
Results: On a single measurement, AGEs were increased in subjects with vs. those without CAN (3.20±0.74 vs. 2.66±0.66, p<0.001). As compared with normal results, AGEs were increased for each one of the 4 abnormal CARTs: Valsalva Ratio (3.36±0.67 vs. 2.66±0.72, p=0.004), E/I ratio (3.01±0.72 vs. 2.53±0.68, p=0.001), 30:15 ratio (3.08±0.76 vs. 2.75±0.69, p=0.011), postural hypotension (3.30±0.72 vs. 2.75±0.66, p<0.001). Similar results were obtained for triplicate measurements.
Discussion: Among T2DM subjects, skin AGEs appear to increase in the presence of CAN. This holds true both for sympathetic and parasympathetic nervous system impairment.
Context: Primary aldosteronism (PA) represents the most frequent cause of endocrine arterial hypertension. PA is also common in patients with mild forms of hypertension and normokalemia.
Objective: To identify the prevalence of PA in newly diagnosed hypertensive patients in primary care in Southern Germany.
Patients and methods: Newly diagnosed hypertensive patients in 27 primary care centers in Munich agreed to participate in the study. Patients were screened for PA using the aldosterone-to-renin ratio (ARR). In case of elevated ARR, confirmation testing was performed. After the diagnosis of PA, subtype differentiation and subsequent therapy of PA were initiated.
Results: A total of 235 patients with newly discovered arterial hypertension were initially screened for PA. Among these, 35 were excluded because the medication indicated pre-existing treated arterial hypertension or they were on interfering antihypertensive medication. At the first screening, 2.0% of the patients had hypokalemia. Of the 200 patients with newly discovered arterial hypertension, 42 had an elevated ARR. The incidence of the presence of hypokalemia did not differ according to normal or pathological ARR. Nine patients (21%) did not show up for further testing and were lost to follow-up, and 33 patients underwent a saline infusion test. Of these, 11 patients were diagnosed with PA, leading to at least 5.5% prevalence of PA in the collective. None of the diagnosed PA patients was hypokalemic at screening.
Conclusion: A 5.5% prevalence of PA was observed in our data of untreated newly diagnosed patients with hypertension.
Dysfunctional eating patterns include alterations in experiencing and expressing hunger, appetite, and satiety, which may lead to eating disorders or obesity in the long term. Alterations in hormones such as ghrelin have been suggested to influence emotional eating in women with obesity. Ghrelin-reactive autoantibodies (autoAbs) are present both in healthy individuals and those with eating disorders and have been suggested to protect the hormone from degradation and preserve its functional activity. This study aimed to evaluate the relationship between IgG ghrelin-reactive autoAbs with dysfunctional eating patterns, subjective perception of stress, and body composition parameters in young women. This cross-sectional study included 82 women (age 21±2 years) classified according to body fat percentage. Dysfunctional eating patterns were measured with the Spanish version of the Three-factor Eating Questionnaire-R18, and perceived stress was measured with the Spanish version of the Perceived Stress Scale - 10. A validated in-house enzyme-linked immunosorbent assay was performed to measure IgG ghrelin-reactive autoAbs in its free, total, and immune complex fractions. Free IgG ghrelin-reactive autoAbs were positively correlated with weight, BMI, body fat percentage, waist, and hip circumference in women with very high body fat percentage. In this group, a negative correlation was observed between ghrelin immune complexes and uncontrolled eating. This exploratory research shows that IgG ghrelin-reactive autoAbs have a potential role in altered body composition parameters and appetite expression, such as uncontrolled eating in women with very high body fat. Further studies are required to clarify the role of IgG autoAbs in eating behavior.
Background: Vascular endothelial function plays an essential role in gestational diabetes mellitus (GDM) pathogenesis. Vascular elasticity is evaluated by the echo-tracking (ET) technique. In this study, we aimed to assess the clinical value of the ET technique in women with GDM and provide a basis for early evaluation and prevention of gestational diabetes.
Methods: Sixty-five patients with GDM and 65 gestational week-matched normal glucose tolerance pregnant women were enrolled in this study. The endothelial function parameters of pressure-strain elasticity coefficient (EP), the common carotid stiffness index (β), arterial compliance (AC), single-point pulsed-wave velocity (PWVβ), and augment index (AI) of bilateral common carotid arteries, were compared between the GDM and control groups by using ET technique. The correlations between plasma glucose levels and ET parameters were also analyzed.
Results: Our results indicated that EP, β, PWVβ, and AI were significantly higher in the GDM group (p<0.05), whereas AC was significantly lower in patients with GDM than in the control group (p<0.001). In addition, fasting plasma glucose and plasma glucose level after 2 h oral glucose tolerance test was correlated with ET parameters of EP, β, PWVβ, AI, and AC.
Conclusions: The application of ET technology to gestational diabetes women could provide a basis for early evaluation and prevention of gestational diabetes. It would detect early and accurate signs of diabetes in pregnant women and provide a timely and reasonable clinical treatment plan to reduce and delay the occurrence of complications.
Objective: To investigate the impact of metabolic status on choroidal thickness (ChT) in healthy subjects, patients with obesity, and type 2 diabetes.
Design and methods: Fasting blood glucose, insulin, insulin-like growth factor-1 (IGF-1), and ChT measured by optical coherence tomography were assessed in healthy normal-weight (n=17), obese participants (n=20), and obese participants with T2D (n=16).
Results: ChT increased in obese participants and obese participants with T2D as compared to healthy normal-weight participants (P<0.0001). A negative correlation was observed between IGF1 and ChT (r=-0.268, P=0.050) for all cohorts. Furthermore, body mass index (BMI; R2=0.209; P=0.002; beta=0.388) and model assessment-estimated insulin resistance (HOMA-IR; R2=0.074; P=0.015; beta=0.305) were independent variables of ChT, explaining 20.9 and 7.4% of its variance (both p<0.016), whereas age, sex, and IGF-1 were not significant confounders of ChT (p>0.975).
Conclusion: ChT is associated with metabolic characteristics, i. e., BMI and HOMA-IR. Due to the key role of choroidal function in retinal physiology, future studies are needed to evaluate whether metabolic traits, ChT, and potential metabolic eye complications are mechanistically linked.
The prevalence of gestational diabetes parallels the prevalence of type 2 diabetes mellitus and is associated with adverse pregnancy outcomes. However, these data are not available for many parts of the world. We assessed the prevalence of gestational diabetes and pregnancy outcomes in Tajikistan. This cohort study included 2438 consecutively recruited representative pregnant women from 8 locations in two cities in Tajikistan, in whom an oral glucose tolerance test (75 g, fasting, 1 h, 2 h) was performed during gestational weeks 24-28. Women with known diabetes and twin pregnancies were excluded. Associations between glucose tolerance test results and pregnancy outcomes were examined. According to the WHO 2013 thresholds, 32.4% of women qualified as having gestational diabetes, the vast majority (29.7%) based on an elevated fasting glucose level (5.1-5.6 mmol/L), while only 2.8% had elevated 1- or 2-hour values or met more than one threshold. Women with only elevated fasting glucose (impaired gestational fasting glycemia) had no evidence of adverse pregnancy outcomes, while those with elevated 1- and/or 2-hour values (impaired gestational glucose tolerance) had more pregnancy complications (infection of urinary tract 1.8 vs. 8.8% p<0.001; preeclampsia 0.7 vs. 10.3% p<0.001) and emergency cesarean sections (4.4 vs. 13.2% p=0.002). Neonates from pregnancies with impaired gestational glucose tolerance had lower APGARs, lower birth weights, lower 30 min glucose levels, and a lower probability of being discharged alive (all p<0.05). In conclusion, the formal prevalence of gestational diabetes is high in Tajikistan; however, this does not translate into adverse pregnancy outcomes for women with impaired gestational fasting glycemia.
Objective: To assess safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with the selective 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) inhibitor BI 187004 in male and female patients with type 2 diabetes and overweight or obesity.
Methods: Randomized, double-blind, parallel-group, placebo-controlled multiple rising dose study, with 10-360 mg BI 187004 once daily over 14 days in 71 patients. Assessments included 11beta-HSD1 inhibition in the liver and subcutaneous adipose tissue ex vivo (clinical trial registry number NCT01874483).
Results: BI 187004 was well tolerated and safe in all tested dose groups. The incidence of drug-related adverse events was 51.8% (n=29) for BI 187004 and 35.7% (n=5) for placebo. There were no clinically relevant deviations in laboratory or electrocardiogram parameters besides one patient on 360 mg discontinuing treatment due to moderate supraventricular tachycardia.BI 187004 was rapidly absorbed within 2 h; exposure increased non-proportionally. The oral clearance was low, apparent volume of distribution was moderate to large, and terminal half-life with 106-124 h was rather long. Urinary tetrahydrocortisol/tetrahydrocortisone ratio decreased, indicating liver 11beta-HSD1 inhibition. Median inhibition of 11beta-HSD1 in subcutaneous adipose tissue biopsies was 87.9-99.4% immediately after the second dose and 73.8-97.5% 24 h after the last dose of BI 187004.
Conclusions: BI 187004 was safe and well tolerated over 14 days and could be dosed once daily. Targeted 11beta-HSD1 enzyme inhibition of≥80% could be shown for BI 187004 doses≥40 mg. This dose should be targeted in further studies to test blood glucose lowering in patients with type 2 diabetes and overweight or obesity.
The consumption of high-fructose corn syrup (HFCS) has been increasing in recent decades, especially among children. Some reports suggest that children and adolescents are more sensitive to the adverse effects of fructose intake than adults. However, the underlying mechanism of the difference in vulnerability between adolescence and adulthood have not yet been elucidated. In this study, we attempted to elucidate the different effects of HFCS intake at different growth stages in rats: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and adulthood (PD100-140). Since alterations in hepatic glucocorticoid (GC) metabolism can cause diseases including insulin resistance, we focused on GC metabolizing enzymes such as 11 beta-hydroxysteroid dehydrogenase 1 and 2 (Hsd11b1 and Hsd11b2) and steroid 5 alpha-reductase 1 (Srd5a1). Western blotting showed an increase in Hsd11b1 expression and a decrease in Hsd11b2 expression in childhood and adolescence but not in adulthood. We also observed changes in Hsd11b1 and Hsd11b2 activities only in childhood and adolescence, consistent with the results of mRNA and protein expression analysis. The effect of high-fructose intake with regards to GC metabolism may therefore vary with developmental stage. This study provides insight into the adverse effects of fructose on GC metabolism in children in the context of increasing rates of HFCS consumption.
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