Pharmacomicrobiomics in Western Medicine and Traditional Chinese Medicine in Type 2 Diabetes.

Pharmacomicrobiomics refers to the interactions between foreign compounds and the gut microbiome resulting in heterogeneous efficacy, side effects, and toxicity of the compound concerned. Glucose lowering drugs reduce blood glucose by modulating insulin secretion and its actions as well as redistributing energy disposal. Apart from genetic, ecological, and lifestyle factors, maintaining an equilibrium of the whole gut microbiome has been shown to improve human health. Microbial fingerprinting using faecal samples indicated an 'invisible phenotype' due to different compositions of microbiota which might orchestrate the interactions between patients' phenotypes and their responses to glucose-lowering drugs. In this article, we summarize the current evidence on differences in composition of gut microbiota between individuals with type 2 diabetes (T2D) and healthy individuals, the disruption of the balance of beneficial and pathogenic microbiota was shown in patients with T2D and how Western Medicine (WM) and Traditional Chinese Medicine (TCM) might re-shape the gut microbiota with benefits to the host immunity and metabolic health. We particularly highlighted the effects of both WM and TCM increase the relative abundance of health promoting bacteria, such as, Akkermansia muciniphila, Blautia, and Bifidobacterium adolescentis, and which have been implicated in type 2 diabetes (T2D). Several lines of evidence suggested that TCM might complement the efficacy of WM through alteration of microbiota which warrants further investigation in our pursuit of prevention and control of T2D.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

A polysaccharide extract from the medicinal plant Maidong inhibits the IKK-NF-κB pathway and IL-1ß-induced islet inflammation and increases insulin secretion.

The herb dwarf lilyturf tuber (Maidong, Ophiopogonis Radix) is widely used in Chinese traditional medicine to manage diabetes and its complications. However, the role of Maidong polysaccharide extract (MPE) in pancreatic ß-cell function is unclear. Here, we investigated whether MPE protects ß-cell function and studied the underlying mechanisms. We treated db/db and high-fat diet (HFD)-induced obese mice with 800 or 400 mg/kg MPE or water for 4 weeks, followed by an oral glucose tolerance test. Pancreas and blood were collected for molecular analyses, and clonal MIN6 ß-cells and primary islets from HFD-induced obese mice and normal chow diet-fed mice were used in additional analyses. In vivo, MPE both increased insulin secretion and reduced blood glucose in the db/db mice but increased only insulin secretion in the HFD-induced obese mice. MPE substantially increased the ß-cell area in both models (3-fold and 2-fold, p < 0.01, for db/db and HFD mice, respectively). We observed reduced nuclear translocation of the p65 subunit of NF-κB in islets of MPE-treated db/db mice, coinciding with enhanced glucose-stimulated insulin secretion (GSIS). In vitro, MPE potentiated GSIS and decreased interleukin 1ß (IL-1ß) secretion in MIN6 ß-cells. Incubation of MIN6 cells with tumor necrosis factor α (TNFα), interferon-γ, and IL-1ß amplified IL-1ß secretion and inhibited GSIS. These effects were partially reversed with MPE or the IκB kinase ß inhibitor PS1145, coinciding with reduced activation of p65 and p-IκB in the NF-κB pathway. We conclude that MPE may have potential for therapeutic development for ß-cell protection.

Depressive Symptoms, Co-Morbidities, and Glycemic Control in Hong Kong Chinese Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Undiagnosed depression is an important comorbidity in type 2 diabetes (T2D) which can be detected using the Geriatric Depression Scale (GDS-15) questionnaire. In this cross-sectional study, we examined the associations of depression using GDS score with control of cardiometabolic risk factors and health status in elderly patients with T2D. SETTING AND PARTICIPANTS: Between February and December 2013, patients aged ≥65 years who underwent structured comprehensive assessment as a quality improvement program at the Diabetes Center of a teaching hospital were invited to complete the GDS-15 questionnaire. MAIN OUTCOME MEASURES: Depression was defined as a GDS score ≥7. Demographic data, prior history of co-morbidities, frequency of self-reported hypoglycemia, and attainment of treatment targets defined as HbA1c, <7%, blood pressure <130/80 mmHg, and LDL-C <2.6 mmol/L were documented. RESULTS: Among 325 participants (65% male, median [interquartile range] age: 69 [8] years), 42 (13%) had depression. Patients with depression had longer disease durations (mean ± SD: 15.1 ± 9.1 vs. 11.6 ± 8.1 years, P = 0.02), more frequent self-reported hypoglycemic events (17 vs. 6%, P = 0.03) and were less likely to attain all three treatment targets (0 vs. 16%, P = 0.004) than those without depression. On multivariable analysis, patients with depression had an odds ratio of 2.84 (95% confidence intervals: 1.35-6.00, P = 0.006) of reporting prior history of co-morbidities. CONCLUSION: In elderly patients with T2D, depression was not uncommon especially in those with poor control of risk factors, hypoglycemia, and co-morbidities. Inclusion of GDS-15 questionnaire during structured assessment for complications and risk factors can identify these high-risk patients for more holistic management of their physical and mental health.

Aspects of Multicomponent Integrated Care Promote Sustained Improvement in Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis.

OBJECTIVE: The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes. RESEARCH DESIGN AND METHODS: We searched PubMed and Ovid MEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality. RESULTS: In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1 mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to -1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L; Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12 months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg, Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]). CONCLUSIONS: Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. METHODS: The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. FINDINGS: Between March 20, 2009, and Oct 23, 2015, 6522 patients were randomly assigned and included in the intention-to-treat population, 3272 assigned to acarbose and 3250 to placebo. Patients were followed up for a median of 5·0 years (IQR 3·4-6·0) in both groups. The primary five-point composite outcome occurred in 470 (14%; 3·33 per 100 person-years) of 3272 acarbose group participants and in 479 (15%; 3·41 per 100 person-years) of 3250 placebo group participants (hazard ratio 0·98; 95% CI 0·86-1·11, p=0·73). No significant differences were seen between treatment groups for the secondary three-point composite outcome, death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, or impaired renal function. Diabetes developed less frequently in the acarbose group (436 [13%] of 3272; 3·17 per 100 person-years) compared with the placebo group (513 [16%] of 3250; 3·84 per 100 person-years; rate ratio 0·82, 95% CI 0·71-0·94, p=0·005). Gastrointestinal disorders were the most common adverse event associated with drug discontinuation or dose changes (215 [7%] of 3263 patients in the acarbose group vs 150 [5%] of 3241 in the placebo group [p=0·0007]; safety population). Numbers of non-cardiovascular deaths (71 [2%] of 3272 vs 56 [2%] of 3250, p=0·19) and cancer deaths (ten [<1%] of 3272 vs 12 [<1%] of 3250, p=0·08) did not differ between groups. INTERPRETATION: In Chinese patients with coronary heart disease and impaired glucose tolerance, acarbose did not reduce the risk of major adverse cardiovascular events, but did reduce the incidence of diabetes. FUNDING: Bayer AG.

Prevention and Care Programs Addressing the Growing Prevalence of Diabetes in China.

According to a 2010 national survey, 11 % of adults in China have diabetes, affecting 109.6 million individuals. The high prevalence of diabetes has been attributed to the aging of the population, the rapid adoption of energy-dense foods, and a reduction in physical activity. Collectively, these secular changes have created an obesogenic environment that can unmask diabetes in subjects with a genetic predisposition. The growing prevalence of maternal obesity, gestational diabetes, childhood obesity, and early-onset disease can lead to premature morbidity and mortality. Rising to meet these public health challenges, researchers in China have conducted randomized studies to demonstrate the benefits of lifestyle modification in preventing diabetes (the Da Qing Study), as well as that of team-based integrated care, using multiple strategies including peer support and information technology, in order to reduce hospitalizations, cardiovascular-renal complications, and premature deaths. With growing evidence supporting the benefits of these diabetes prevention and management programs, the next challenge is to use policies and systems to scale up the implementation of these programs through raising awareness, building capacity, and providing resources to reduce the human and socioeconomic burden of diabetes.

Selenium-enriched Spirulina protects INS-1E pancreatic beta cells from human islet amyloid polypeptide-induced apoptosis through suppression of ROS-mediated mitochondrial dysfunction and PI3/AKT pathway.

PURPOSE: Human islet amyloid polypeptide (hIAPP) aggregation is linked to loss of pancreatic beta cells in type 2 diabetes, in part due to oxidative stress. Currently, little is known about the effects of selenium-enriched Spirulina on beta cells with the presence of hIAPP. In this study, INS-1E rat insulinoma cells were used as a model to evaluate in vitro protective effects of Se-enriched Spirulina extract (Se-SE) against hIAPP-induced cell death, as well as the underlying mechanisms. METHODS: Flow cytometric analysis was used to evaluate cell apoptosis, mitochondrial membrane potential (ΔΨm) and ROS generation. Caspase activity was measured using a fluorometric method. Western blotting was applied to detect protein expression. RESULTS: Our results showed that exposure of INS-1E cells to hIAPP resulted in cell viability loss, LDH release and appearance of sub-G peak. However, cytotoxicity of hIAPP was significantly attenuated by co-treatment with Se-SE. Se-SE also inhibited hIAPP-induced activation of caspase-3, -8 and -9. Additionally, hIAPP-induced accumulation of ROS and superoxide was suppressed by co-treatment with Se-SE. Moreover, Se-SE was able to prevent hIAPP-induced depletion of ΔΨm and intracellular ATP, reduction in mitochondrial mass, changes in the expression of Bcl-2 family members, release of mitochondrial apoptogenic factors. Furthermore, hIAPP-mediated AKT inhibition was restored by co-treatment with Se-SE. CONCLUSION: Our results showed that Se-SE protects INS-1E cells from hIAPP-induced cell death through preventing ROS overproduction, mitochondrial dysfunction and modulating PI3K/AKT pathway.

Rationale for and design of the Acarbose Cardiovascular Evaluation (ACE) trial.

Patients with cardiovascular disease and impaired glucose tolerance are at increased risk of cardiovascular events and type 2 diabetes mellitus (T2DM). Lifestyle modification or pharmacological intervention can delay progression to T2DM, but there is no clear evidence that they reduce cardiovascular risk in this population. Acarbose, an α-glucosidase inhibitor that lowers postprandial blood glucose, has been shown to reduce T2DM risk by 25%, and possibly cardiovascular risk in impaired glucose tolerance subjects without cardiovascular disease.

A randomized controlled trial to investigate the impact of a low glycemic index (GI) diet on body mass index in obese adolescents.

BACKGROUND: The role of a low glycemic index (GI) diet in the management of adolescent obesity remains controversial. In this study, we aim to evaluate the impact of low GI diet versus a conventional Chinese diet on the body mass index (BMI) and other obesity indices of obese adolescents. METHODS: Obese adolescents aged 15-18 years were identified from population-recruited, territory-wide surveys. Obesity was defined as BMI ≥95th percentile of Hong Kong local age- and sex-specific references. Eligible subjects were randomized to either an intervention with low GI diet (consisting of 45-50% carbohydrate, 30-35% fat and 15-20% protein) or conventional Chinese diet as control (consisting of 55-60% carbohydrate, 25-30% fat and 10-15% protein). We used random intercept mixed effects model to compare the differential changes across the time points from baseline to month 6 between the 2 groups. RESULTS: 104 obese adolescents were recruited (52 in low GI group and 52 in control group; 43.3% boys). Mean age was 16.7 ± 1.0 years and 16.8 ±1.0 years in low GI and control group respectively. 58.7% subjects completed the study at 6 months (65.4% in low GI group and 51.9% in control group). After adjustment for age and sex, subjects in the low GI group had a significantly greater reduction in obesity indices including BMI, body weight and waist circumference (WC) compared to subjects in the control group (all p <0.05). After further adjustment for physical activity levels, WC was found to be significantly lower in the low GI group compared to the conventional group (p = 0.018). CONCLUSION: Low GI diet in the context of a comprehensive lifestyle modification program may be an alternative to conventional diet in the management of obese adolescents. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Ref. No: NCT01278563.

Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study.

BACKGROUND: In the present study, we examined the effect of a two-herb traditional Chinese medicine (NF3), comprised of Astragali Radix and Radix Rehmanniae, on the healing of diabetic foot ulcer and the possible molecular mechanisms involved. METHODS: This was a prospective randomized double-blind placebo-controlled study. Sixteen diabetic patients were randomized to receive either placebo or NF3 for 6 months. Ulcer healing and sensory changes were examined. Molecular studies included measurement of serum tumor necrosis factor (TNF)-α and RNA microarray investigation. RESULTS: The daily rate of reduction in ulcer area was 3.55% in the NF3 group and 1.52% in the placebo group (P = 0.062). In the index limb, the number of negative tests for sensory neuropathy using monofilament was reduced from 27% to 7% in the NF3 group and from 37% to 35% in the placebo group (P < 0.001). In addition, NF3 significantly decreased serum TNF-α levels (P = 0.034). Microarray studies revealed concerted changes following NF3 treatment in the expression of genes implicated in fibroblast regeneration, angiogenesis, and anti-inflammation. CONCLUSIONS: In this proof-of-concept study, 6-month treatment with NF3 was associated with improved wound healing and sensation accompanied by concerted changes in gene expression.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable.

Co-occurrence of diabetes and depression: conceptual considerations for an emerging global health challenge.

BACKGROUND: Considering the relationships between diabetes and depression may enhance programs to reduce their individual and shared disease burden. METHODS: This paper discusses relationships between diabetes and depression, the range of influences on each, conceptual issues central to their definition, and interventions including comprehensive, population approaches to their prevention and management. Foundational and exemplary literature was identified by the writing team according to their areas of expertise. RESULTS: Diabetes and depression influence each other while sharing a broad range of biological, psychological, socioeconomic and cultural determinants. They may be viewed as: (a) distinct but sometimes comorbid entities, (b) dimensions, (c) parts of broader categories, e.g., metabolic/cardiovascular abnormalities or negative emotions, or (d) integrated so that comprehensive treatment of diabetes includes depression or negative emotions, and that of depression routinely considers possible diabetes or other chronic diseases. LIMITATIONS: The choice of literature relied primarily on the authors' knowledge of the issues addressed. Some important perspectives and research may have been overlooked. CONCLUSIONS AND CLINICAL IMPLICATIONS: Collaboration among primary care and specialist clinicians as well as program and public health managers should reflect the commonalities among diabetes, depression, and other chronic mental and physical disorders. Interventions should include integrated clinical care and self-management programs along with population approaches to prevention and management. Self management and problem solving may provide a coherent framework for integrating the diverse tasks and objectives of those living with diabetes and depression or many other varieties of multi-morbidity.

Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine through regulation of hepatic gene expression.

Diabetes and obesity are complex diseases associated with insulin resistance and fatty liver. The latter is characterized by dysregulation of the Akt, AMP-activated protein kinase (AMPK), and IGF-I pathways and expression of microRNAs (miRNAs). In China, multicomponent traditional Chinese medicine (TCM) has been used to treat diabetes for centuries. In this study, we used a three-herb, berberine-containing TCM to treat male Zucker diabetic fatty rats. TCM showed sustained glucose-lowering effects for 1 week after a single-dose treatment. Two-week treatment attenuated insulin resistance and fatty degeneration, with hepatocyte regeneration lasting for 1 month posttreatment. These beneficial effects persisted for 1 year after 1-month treatment. Two-week treatment with TCM was associated with activation of AMPK, Akt, and insulin-like growth factor-binding protein (IGFBP)1 pathways, with downregulation of miR29-b and expression of a gene network implicated in cell cycle, intermediary, and NADPH metabolism with normalization of CYP7a1 and IGFBP1 expression. These concerted changes in mRNA, miRNA, and proteins may explain the sustained effects of TCM in favor of cell survival, increased glucose uptake, and lipid oxidation/catabolism with improved insulin sensitivity and liver regeneration. These novel findings suggest that multicomponent TCM may be a useful tool to unravel genome regulation and expression in complex diseases.

Traditional Chinese medicine in the treatment of diabetes.

This review focuses on the efficacy and safety of Chinese medicine in the treatment of type-2 diabetes. Included were 84 controlled clinical studies of type-2 diabetes treated with Chinese medicine for at least 1 month. Reported outcomes were: symptom relief; improvement in glycemia, insulin resistance and secondary failure, and adverse events. Symptom relief was achieved in most (>80%) of the patients receiving Chinese medicine. Compared with orthodox drugs, Chinese medicine had a 1.2-fold (95% CI 1.2-1.3) increase in symptom relief. The relative risk of achieving a fasting blood glucose of <7.3 mmol/l or a postprandial blood glucose of <8.2 mmol/l was: 3.0 (95% CI 1.4-6.5) for Chinese medicine plus diet versus diet; 2.0 (95% CI 1.4-3.0) for Chinese medicine versus placebo; 1.8 (95% CI 1.4-2.3) for combined Chinese medicine and orthodox drugs versus Yuquan Wan (a classic Chinese herbal formula for diabetes), 1.5 (95% CI 1.4-1.7) for combined Chinese medicine and orthodox drugs vs. orthodox drugs, and 1.3 (95% CI 1.2-1.5) for Chinese medicine versus orthodox drugs. A fasting blood glucose of <8.2 mmol/l plus symptom relief was observed in 71-100% of the patients with secondary failure to oral anti-diabetic drugs. Serious adverse events including hypoglycemic coma and death were caused by adulteration with orthodox drugs, erroneous substitution, self-meditation, overdoses, and improper preparation. Chinese herbal medicine should be used cautiously with doctors' prescription and follow-up. Long-term clinical studies may disclose the effectiveness of Chinese medicine in reducing the mortality and morbidity of diabetic complications.

Effects of protocol-driven care versus usual outpatient clinic care on survival rates in patients with type 2 diabetes.

OBJECTIVE: To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care. STUDY DESIGN: Descriptive analysis of a prospective cohort. PATIENTS AND METHODS: During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records. RESULTS: Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%). CONCLUSION: Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.

Acarbose improves glycemic control in insulin-treated Asian type 2 diabetic patients: results from a multinational, placebo-controlled study.

The purpose of the study was to determine the efficacy and tolerability of acarbose in Asian type 2 diabetic patients insufficiently controlled by insulin. Asian type 2 diabetic patients on stable insulin dosages were enrolled into a multinational, double-blind, placebo-controlled parallel arm study. After a 2-week screening phase, patients were randomly assigned to 50 mg acarbose t.i.d. or matching placebo for 6 weeks, followed by 100 mg acarbose t.i.d. or placebo for 12 weeks. The primary efficacy parameter was change from baseline in HbA(1c); secondary variables included the changes in fasting and postprandial blood glucose. After 18 weeks of treatment there was a difference in HbA(1c) levels between the two treatment groups (-0.69%, 95% CI (-1.18; -0.2), P=0.008) in favour of acarbose. Reductions in 1-h postprandial glucose levels from baseline to endpoint were observed with acarbose treatment (P=0.029). There were no differences in fasting blood glucose, total triglyceride and cholesterol between the two groups. Safety profiles were similar for both treatment arms except for the higher incidence of flatulence in the acarbose group (28.6% vs. 16.4% for placebo). Adjunctive acarbose therapy offers an efficacious and safe means for improvement of glycemic control in Asian type 2 diabetic patients insufficiently controlled by insulin.