Kitty K.T. Cheung

Premature mortality and comorbidities in young-onset diabetes: a 7-year prospective analysis.

BACKGROUND There is an increasing prevalence of young-onset diabetes, especially in developing areas. We compared the clinical outcomes and predictors for cardiovascular-renal events between Chinese patients with type 2 diabetes with young- or late-onset of disease diagnosed before or after the age of 40 years, respectively. METHODS The Hong Kong Diabetes Registry was established in 1995 as an ongoing quality improvement initiative with consecutive enrollment of diabetic patients from ambulatory settings for documentation of risk factors, microvascular and macrovascular complications, and clinical outcomes using a structured protocol. RESULTS In 9509 Chinese patients with type 2 diabetes with a median (interquartile range) follow-up period of 7.5 (3.9-10.8) years, 21.3% (n = 2066) had young-onset diabetes. Despite 20 years difference in age, patients with young-onset diabetes (mean age, 41.3 years) had a similar or worse risk profile than those with late-onset disease (mean age, 61.9 years). Compared with the patients with late-onset diabetes, those with young-onset diabetes had lower rates of cardiovascular disease and chronic kidney disease for the same disease duration but a higher cumulative incidence of clinical events at any given age. With the use of stepwise Cox proportional hazard analysis, patients with young-onset diabetes had higher risks for cardiovascular and renal events when adjusted by age, but no difference in risks than in the patients with late-onset diabetes when further adjusted by disease duration. CONCLUSIONS Patients with young-onset diabetes had a similar or worse metabolic risk profile compared with those with late-onset disease. This group had higher risks for cardiovascular-renal complications at any given age, driven by longer disease duration.

Severe Hypoglycemia Identifies Vulnerable Patients With Type 2 Diabetes at Risk for Premature Death and All-Site Cancer: The Hong Kong Diabetes Registry

OBJECTIVE We examined the associations of clinical profiles in type 2 diabetic patients who developed severe hypoglycemia and their clinical outcomes, including death and all-site cancer. RESEARCH DESIGN AND METHODS A consecutive cohort of 8,767 type 2 diabetic patients with and without severe hypoglycemia in the 12 months before enrollment were recruited between 1995 and 2007, with follow-up until 2009. Severe hypoglycemia was defined by ICD-9 codes as hospitalizations resulting from hypoglycemia. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% CIs of clinical factors collected at enrollment for severe hypoglycemia. RESULTS In this cohort, mean age was 57.4 (SD 13.2) years and median disease duration of diabetes was 5 (interquartile range [IQR] 1–11) years. During a median follow-up of 6.71 (IQR 3.47–10.38) years, 235 patients had severe hypoglycemia (incidence 3.96 [95% CI 3.45–4.46] per 1,000 patient-years). At enrollment, patients with and without severe hypoglycemia had similar cancer rates. During follow-up, patients with severe hypoglycemia had a higher incidence of all-site cancer (13.4 vs. 6.4%, P < 0.0001) and mortality (32.8 vs. 11.2%, P < 0.0001) than those without severe hypoglycemia. After adjusting for confounders, old age, low BMI, high glycated hemoglobin, low triglyceride (TG), low LDL cholesterol (LDL-C), albuminuria, and chronic kidney disease were independent predictors for severe hypoglycemia. CONCLUSIONS In type 2 diabetes, severe hypoglycemia is associated with advanced age, renal dysfunction, poor glycemic control, and cancer subphenotypes (low BMI, low LDL-C, and low TG).

Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome

Objective Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. Design Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. Results Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. Conclusions In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. Trial registration number NCT02570477

Anti-inflammatory effects of exendin-4, a glucagon-like peptide-1 analog, on human peripheral lymphocytes in patients with type 2 diabetes

Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon‐like peptide (GLP‐1) might have immunomodulating effects. We hypothesize that GLP‐1 receptor agonist, exendin‐4, might reduce inflammatory response in type 2 diabetes.

A New Tool to Detect Kidney Disease in Chinese Type 2 Diabetes Patients—Comparison of EZSCAN with Standard Screening Methods

BACKGROUND EZSCAN(®) (Impeto Medical, Paris, France), a noninvasive device that assesses sweat gland dysfunction using reverse iontophoresis, also detects early dysglycemia. Given the interrelationships among dysglycemia, vasculopathy, and neuropathy, EZSCAN may detect kidney disease in diabetes (DKD). METHODS An EZSCAN score (0-100) was calculated using a proprietary algorithm based on the chronoamperometry analysis. We measured the score in 50 Chinese type 2 diabetes patients without DKD (urinary albumin-creatinine ratio [ACR] <2.5 mg/mmol in men or ACR <3.5 mg/mmol in women and estimated glomerular filtration rate [eGFR] >90 mL/min/1.73 m(2)) and 50 with DKD (ACR ≥25 mg/mmol and eGFR <60 mL/min/1.73 m(2)). We used spline analysis to determine the threshold value of the score in detecting DKD and its sensitivity and specificity. RESULTS EZSCAN scores were highly correlated with log values of eGFR (r=0.67, P<0.0001) and ACR (r=-0.66, P<0.0001). Using a cutoff value of 55, the score had 94% sensitivity, 78% specificity, and a likelihood ratio of 4.2 to detect DKD with a positive predictive value of 81% and a negative predictive value of 93%. On multivariable analysis, DKD was independently associated with EZSCAN score (β=-0.72, P=0.02), smoking status (1=never, 0=current/former) (β=-2.37, P=0.02), retinopathy (1=yes, 0=no) (β=3.019, P=0.01), triglycerides (β=2.56, P=0.013), and blood hemoglobin (β=-0.613, P=0.04). Patients without DKD but low EZSCAN score (n=10) had longer duration of disease (median [interquartile range], 13 [9-17] vs. 8 [4-16] years; P=0.017) and were more likely to have retinopathy (36.7% vs. 5.1%, P=0.02), lower eGFR (98 [95.00-103] vs. 106 [98.5-115], P=0.036), and treatment with renin-angiotensin system blockers (81.8% vs. 25.6%, P=0.002) than those with a normal score. CONCLUSION EZSCAN may detect high-risk subjects for DKD in Chinese populations.

Additive effects of blood glucose lowering drugs, statins and renin-angiotensin system blockers on all-site cancer risk in patients with type 2 diabetes

BackgroundHyperglycemia is associated with increased risk of all-site cancer that may be mediated through activation of the renin-angiotensin-system (RAS) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A-reductase (HMGCR) pathways. We examined the joint associations of optimal glycemic control (HbA1c <7%), RAS inhibitors and HMGCR inhibitors on cancer incidence in patients with type 2 diabetes.MethodsPatients with type 2 diabetes, with or without a history of cancer or prior exposure to RAS or HMGCR inhibitors at baseline were observed between 1996 and 2005. All patients underwent a comprehensive assessment at baseline and were followed until the censored date at 2005 or their death.ResultsAfter a median follow-up period of 4.91 years (interquartile range, 2.81 to 6.98), 271 out of 6,103 patients developed all-site cancer. At baseline, patients with incident cancers were older, had longer disease duration of diabetes, higher alcohol and tobacco use, and higher systolic blood pressure and albuminuria, but lower triglyceride levels and estimated glomerular filtration rate (P <0.05). Patients who developed cancers during follow-up were less likely to have started using statins (22.5% versus 38.6%, P <0.001), fibrates (5.9% versus 10.2%, P = 0.02), metformin (63.8% versus 74.5%, P <0.001) or thiazolidinedione (0.7% versus 6.8%, P <0.001) than those who remained cancer-free. After adjusting for co-variables, new treatment with metformin (hazard ratio: 0.39; 95% confidence interval: 0.25, 0.61; P <0.001), thiazolidinedione (0.18; 0.04, 0.72; P = 0.015), sulphonylurea (0.44; 0.27, 0.73; P = 0.014), insulin (0.58; 0.38, 0.89; P = 0.01), statins (0.47; 0.31, 0.70; P <0.001) and RAS inhibitors (0.55; 0.39, 0.78; P <0.001) were associated with reduced cancer risk. Patients with all three risk factors of HbA1c ≥7%, non-use of RAS inhibitors and non-use of statins had four-fold adjusted higher risk of cancer than those without any risk factors (incidence per 1,000-person-years for no risk factors: 3.40 (0.07, 6.72); one risk factor: 6.34 (4.19, 8.50); two risk factors: 8.40 (6.60, 10.20); three risk factors: 13.08 (9.82, 16.34); P <0.001).ConclusionsHyperglycemia may promote cancer growth that can be attenuated by optimal glycemic control and inhibition of the RAS and HMGCR pathways.

Hypoglycaemia, chronic kidney disease and death in type 2 diabetes: the Hong Kong diabetes registry

BackgroundIn patients with type 2 diabetes, chronic kidney disease (CKD) is associated with increased risk of hypoglycaemia and death. Yet, it remains uncertain whether hypoglycaemia-associated mortality is modified by CKD.MethodsType 2 diabetic patients, with or without CKD at enrolment were observed between 1995 and 2007, and followed up till 2009 at hospital medical clinics. We used additive interaction, estimated by relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP) to examine possible synergistic effects between CKD and severe hypoglycaemia (defined as hospitalisations due to hypoglycaemia in the 12 months prior to enrolment) on the risk of death.ResultsIn this cohort of 8,767 type 2 diabetic patients [median age: 58 (interquartile range: 48 to 68) years; disease duration: 5 (1 to 11) years, men: 47.0%], 1,070 (12.2%) had died during a median follow-up period of 6.66 years (3.42-10.36) with 60,379 person-years.Upon enrolment, 209 patients had severe hypoglycaemia and 194 developed severe hypoglycaemia during follow-up (15 patients had both). In multivariable analysis and using patients without severe hypoglycaemia nor CKD as the referent group (683 deaths in 7,598 patients), severe hypoglycaemia alone (61 deaths in 272 patients) or CKD alone (267 death in 781 patients) were associated with increased risk of death [Hazard ratio, HR: 1.81(95%CI: 1.38 to 2.37) and 1.63 (1.38 to 1.93) respectively]. Having both risk factors (59 deaths in 116 patients) greatly enhanced the HR of death to 3.91 (2.93 to 5.21) with significant interaction (RERI: 1.46 and AP: 0.37, both p-values < 0.05).ConclusionsSevere hypoglycaemia and CKD interact to increase risk of death in type 2 diabetes patients.

Modifying Effect of Body Mass Index on Survival in Elderly Type 2 Diabetic Patients: Hong Kong Diabetes Registry

OBJECTIVE There are nonlinear risk associations of body mass index (BMI) with mortality in type 2 diabetes (T2D) and elderly populations although similar information in elderly individuals with T2D are lacking. RESEARCH DESIGN AND METHODS We analyzed prospective data for 3186 Chinese patients with T2D with age 65 years or older. Baseline demographic data, risk factors, complications, and all-cause mortality were captured from the Hong Kong Diabetes Registry and the Hong Kong Hospital Authority Clinical Management System. RESULTS Over a median follow-up period of 6.0 years (medium-term), 816 (25.6%) deaths occurred and at 9.4 years (long-term), 1557 (48.9%) patients had died. Men were more likely to die than women with increased mortality rate with increasing age (morality rates of men with normal BMI at 9-year follow-up in the 65 to 69, 70 to 74, and 75 years or older age groups were 41.8, 70.3, and 101.4 per 1000 person-years, whereas that for women were 35.5, 50.4, and 78.8 respectively). Within each age group, high BMI was associated with increased survival, especially in the 75 years and older age group and with prolonged follow-up period. Using Cox regression analysis, after adjustment for confounders, high BMI (≥ 25.0 kg/m(2)) was associated with reduced risk of death in all subgroups, reaching significance in men in the older age groups at 9-year follow-up (for men 70 to 74 years old, hazard ratio [HR] of mortality was 0.67, 95% confidence interval [CI] 0.48-0.95, for those ≥ 75, HR was 0.62, 95% CI 0.44-0.89) compared with 18.5 to 22.9 kg/m(2) as referent. CONCLUSIONS In Chinese elderly patients with T2D, high BMI protected against mortality, calling for more attention to people with low BMI who might have unmet clinical needs.

Intrarenal arterial resistance is associated with microvascular complications in Chinese type 2 diabetic patients

BACKGROUND Increased renal arterial resistance is associated with various types of chronic renal parenchymal diseases. A resistance index (RI) > 0.8 predicts deterioration in renal function in diabetic subjects. However, the association between renal RI and other diabetic complications has not been investigated. In this study, we examined the association between intrarenal arterial RI and diabetic complications in Chinese type 2 diabetic subjects. METHODS Three hundred and eighty-seven Chinese type 2 diabetic patients were recruited from a structured assessment programme to evaluate their risk factors and complications as a part of the quality improvement programme at the Prince of Wales Hospital. All subjects underwent ultrasound examinations for the assessment of intrarenal arterial RI of both kidneys. Clinical and biochemical parameters, including diabetes-related microvascular complications (nephropathy, retinopathy and sensory neuropathy) and macrovascular diseases, were examined. RESULTS The mean RI of patients with any microvascular complications (0.70 ± 0.09 versus 0.65 ± 0.06) such as nephropathy (0.71 ± 0.09 versus 0.66 ± 0.06), retinopathy (0.71 ± 0.08 versus 0.67 ± 0.08) and sensory neuropathy (0.75 ± 0.07 versus 0.68 ± 0.08) and with any macrovascular complications (0.71 ± 0.09 versus 0.68 ± 0.08) was higher than those without (P < 0.05). On multivariate analysis, after controlling for confounding variables, an RI ≥0.75 was associated with microvascular complications, nephropathy, retinopathy and sensory neuropathy, with odds ratio of 4.02 [95% confidence interval (CI) 1.72-9.4], 4.99 (2.61-9.56), 2.78 (1.52-5.09) and 5.74 (1.8-18.3), respectively. The association of RI with macrovascular complications was not significant in multivariate analysis. CONCLUSION Increased intrarenal arterial resistance was independently associated with an increased risk of microvascular complications including diabetic nephropathy, diabetic retinopathy and diabetic sensory neuropathy in Chinese type 2 diabetic patients.

Life-threatening hypokalemic paralysis in a young bodybuilder.

We report a case of life-threatening hypokalemia in a 28-year-old bodybuilder who presented with sudden onset bilateral lower limbs paralysis few days after his bodybuilding competition. His electrocardiogram (ECG) showed typical u-waves due to severe hypokalemia (serum potassium 1.6 mmol/L, reference range (RR) 3.5–5.0 mmol/L). He was admitted to the intensive care unit (ICU) and was treated with potassium replacement. The patient later admitted that he had exposed himself to weight loss agents of unknown nature, purchased online, and large carbohydrate loads in preparation for the competition. He made a full recovery after a few days and discharged himself from the hospital against medical advice. The severe hypokalemia was thought to be caused by several mechanisms to be discussed in this report. With the ever rising number of new fitness centers recently, the ease of online purchasing of almost any drug, and the increasing numbers of youngsters getting into the bodybuilding arena, clinicians should be able to recognize the possible causes of sudden severe hypokalemia in these patients in order to revert the pathophysiology.