Yan-Mei Huang

Neuroendocrine hormone amylin in diabetes.

The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and co-secreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes.

A meta-analysis of renal outcomes in living kidney donors.

AbstractGiven the increased burden of end-stage renal disease (ESRD), renal outcomes of kidney donation by living donors are of particular interest. PubMed, ProQuest, MEDLINE, EMBASE, Chinese national knowledge infrastructure, and Wanfang databases were searched for clinical outcomes of living kidney donors (LKDs) including renal death, ESRD, proteinuria/albuminuria, and renal function after donation. We included 62 studies from 19 countries involving 114,783 kidney donors and nondonors to evaluate the renal consequences less than 6 months, 6 months to 5 years, 5 to 10 years, and 10 years onward after donation. The pooled data showed that uninephrectomy significantly decreased glomerular filtration rate and creatinine clearance rate in parallel with increased serum creatinine concentration (all P < 0.05). The drastic changes in renal function occurred within 6 months rather than 5 to 10 years after donation. Ten years and onward, rate of proteinuria/albuminuria increased gradually: microalbuminuria from 5.3% to 20.9%, proteinuria from 4.7% to 18.9%, and overt proteinuria from 2.4% to 5.7% (all P < 0.05). Prevalence of ESRD was 1.1%. All-cause mortality was 3.8% and all the renal deaths on average occurred 10 years postnephrectomy. LKDs might have aggravated glomerular filtration and creatinine clearance within 6 months after donation. Five years and onward, albuminuria, proteinuria, ESRD, and death might be the major concerns of LKDs. Long-term studies may clarify the survival time after donation.

Renin–angiotensin system blockade for the risk of cancer and death

Introduction: The effects of renin–angiotensin system blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent. Methods: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case–control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer. Results: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73–0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92–1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75–0.97) but not for other sites of cancer. The relative risk of cancer associated with renin–angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55–0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89–1.09). Conclusions: The significant benefits of renin–angiotensin system blockade observed in case–control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes.

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi’s sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

Cross-talk between AMP-activated protein kinase and renin–angiotensin system in uninephrectomised rats

Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats.

Efficacy and safety of pramlintide injection adjunct to insulin therapy in patients with type 1 diabetes mellitus: a systematic review and meta-analysis

Aims We aim to assess the efficacy and safety of pramlintide plus insulin therapy in patients with type 1 diabetes. Methods We included clinical studies comparing pramlintide plus insulin to placebo plus insulin. Efficacy was reflected by glycemic control and reduction in body weight and insulin use. Safety concerns were hypoglycemia and other adverse events. Subgroup analysis was performed for different doses (30, 60, 90 µg/meal) and durations (≤4, 26, 29, >29 weeks) of the treatment. Results A total of 10 randomized placebo-controlled studies were included for this meta-analysis (pramlintide, n=1978; placebo, n=1319). Compared with controls, patients given pramlintide had significantly lower HbA1c (p < 0.001), total daily insulin dose (p = 0.024), mean mealtime insulin dose (p < 0.001), body weight (p < 0.001) and postprandial glucose level (p = 0.002). The addition of pramlintide increased the incidence of nausea (p < 0.001), vomiting (p < 0.001), anorexia (p < 0.001) and hypoglycemia (p < 0.05) at the initiation of the treatment. The efficacy and adverse reactions of pramlintide were largely significant for the different doses and durations of the treatment. Conclusions The addition of pramlintide to insulin therapy in patients with type 1 diabetes improves glycemic control and reduces insulin requirement and body weight while bringing transient hypoglycemia and digestive disorders.AIMS We aim to assess the efficacy and safety of pramlintide plus insulin therapy in patients with type 1 diabetes. METHODS We included clinical studies comparing pramlintide plus insulin to placebo plus insulin. Efficacy was reflected by glycemic control and reduction in body weight and insulin use. Safety concerns were hypoglycemia and other adverse events. Subgroup analysis was performed for different doses (30, 60, 90 µg/meal) and durations (≤4, 26, 29, >29 weeks) of the treatment. RESULTS A total of 10 randomized placebo-controlled studies were included for this meta-analysis (pramlintide, n=1978; placebo, n=1319). Compared with controls, patients given pramlintide had significantly lower HbA1c (p < 0.001), total daily insulin dose (p = 0.024), mean mealtime insulin dose (p < 0.001), body weight (p < 0.001) and postprandial glucose level (p = 0.002). The addition of pramlintide increased the incidence of nausea (p < 0.001), vomiting (p < 0.001), anorexia (p < 0.001) and hypoglycemia (p < 0.05) at the initiation of the treatment. The efficacy and adverse reactions of pramlintide were largely significant for the different doses and durations of the treatment. CONCLUSIONS The addition of pramlintide to insulin therapy in patients with type 1 diabetes improves glycemic control and reduces insulin requirement and body weight while bringing transient hypoglycemia and digestive disorders.

ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus

Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients (P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P < 0.050). Hyperglycemia, hypertension, and dyslipidemia in these T2DM patients were found to be significantly associated with BMI. In conclusion, the relationship of ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers.

Sudden Deaths Among Chinese Physicians

IntroductIon Sudden deaths are always an important topic, which catches physicians and health professionals’ attention. Physicians and clinical scientists have reported their findings of unexpected deaths concerning about infants, children, young athletes, soldiers, adults with chronic diseases, and elderly people in thousands, if not millions of publications.[1,2] However, there are no existing clinical reports about sudden deaths among physicians and medical staff. Recently, sudden deaths in Chinese physicians, anesthesiologists in particular, become the headlines in media and news. Chinese physicians are turning into the high‐risk professionals of sudden death during the hospital duty hours. According to an official survey, there are a total of 984,926 medical institutions and more than 97 million physicians in China by the end of 2014, while the annual medical graduates and postgraduates amount nearly 600,000 (http://yyh. dxy.cn/article/105034). With the rapid growth of Chinese economy and the radical upheaval of expanding hospital size, sudden deaths in Chinese physicians become critical social issues and contemporary health problems, challenging medical education and hospital management. Hereby, we have investigated the issues and problems of sudden deaths in Chinese physicians for the purpose of self‐alert, self‐protection, and self‐life‐saving.

Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease.

Introduction: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe. Methods: Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough. Results: Eight meta-analyses included 2177–61,264 patients with follow-up of 6–108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86–0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79–0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73–0.87), ACEis (RR, 0.79, 95% , 0.64–0.94), and both (RR, 0.79, 95% CI, 0.73–0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13–5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75–3.22) Conclusions: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection.

Characteristic patterns of normal meridian acupoint temperature

Background Body temperature is an important indicator of health and illness. However, a single temperature measurement is not always reliable. Such measurements can be made using meridians, which are energy channels with acupoints being the nodes. To date, there is no published reference of meridian acupoint temperatures applicable to human health, and there is no clear digitalized indicator that could be utilized to evaluate human health by way of meridian acupoints up to now. Methods Our study recruited 100 healthy medical college students for the measurement of acupoint temperature. The temperatures of 135 acupoints of 14 main meridians were measured using infrared thermometers in order to provide a comprehensive body temperature reading of each study participant. Results The degree of the acupoint temperature consistently ranged from 34.88°C to 36.14°C. The gross thermograph was concentric, with high degree readings around the heart and low degree readings originating from the feet. The left and right body sides had significant correlation between the degrees of bilateral same name acupoint temperatures of 12 regular meridians (correlation coefficient, 0.367–0.985; p < 0.0001). There was also a significant correlation between the acupoint temperature for the governor vessel and the conception vessel (correlation coefficient, 0.083; p = 0.006). Conclusion These findings indicate that meridian acupoint temperature is characterized by a consistently narrow range, as well as concentricity and symmetry in body temperature degree readings in college students. Meridian acupoint temperature may be a sensitive and valuable indicator to assist in the accurate evaluation of meridian and general human health, and the significance and changes of acupoint temperature in clinical conditions warrants future exploration.