A data-driven model for COVID-19 pandemic - Evolution of the attack rate and prognosis for Brazil.

We introduce a compartmental model SEIAHRV (Susceptible, Exposed, Infected, Asymptomatic, Hospitalized, Recovered, Vaccinated) with age structure for the spread of the SARAS-CoV virus. In order to model current different vaccines we use compartments for individuals vaccinated with one and two doses without vaccine failure and a compartment for vaccinated individual with vaccine failure. The model allows to consider any number of different vaccines with different efficacies and delays between doses. Contacts among age groups are modeled by a contact matrix and the contagion matrix is obtained from a probability of contagion p c per contact. The model uses known epidemiological parameters and the time dependent probability p c is obtained by fitting the model output to the series of deaths in each locality, and reflects non-pharmaceutical interventions. As a benchmark the output of the model is compared to two good quality serological surveys, and applied to study the evolution of the COVID-19 pandemic in the main Brazilian cities with a total population of more than one million. We also discuss with some detail the case of the city of Manaus which raised special attention due to a previous report of We also estimate the attack rate, the total proportion of cases (symptomatic and asymptomatic) with respect to the total population, for all Brazilian states since the beginning of the COVID-19 pandemic. We argue that the model present here is relevant to assessing present policies not only in Brazil but also in any place where good serological surveys are not available.

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.

High risk of conversion to diabetes in first-degree relatives of individuals with young-onset type 2 diabetes: a 12-year follow-up analysis.

AIM: Family history of diabetes is an established risk factor for Type 2 diabetes, but the impact of a family history of young-onset diabetes (onset < 40 years) on future risk of diabetes among first-degree relatives is unclear. In this prospective study, we examined the influence of family history of late- versus young-onset diabetes on the development of diabetes in a young to middle-aged Chinese population. METHODS: Some 365 siblings identified through probands with Type 2 diabetes and 452 participants from a community-based health awareness project (aged 18-55 years) who underwent metabolic assessment during the period 1998-2002 were followed to 2012-2013 to determine their glycaemic status. Multivariate logistic regression was performed to investigate the association of family history of diabetes presented at different age categories with development of diabetes. RESULTS: In this cohort, 53.4% (n = 167) of participants with a family history of young-onset diabetes, 30.1% (n = 68) of those with a family history of late-onset diabetes and 14.4% (n = 40) of those without a family history developed diabetes. Using logistic regression, family history of diabetes presented at ages ≥ 50, 40-49, 30-39 and < 30 years, increased conversion to diabetes with respective odds ratios of 2.4, 5.8, 9.4 and 7.0 (P < 0.001 for all), after adjustment for socio-economic status, smoking, obesity, hypertension and dyslipidaemia. Among participants without diabetes at baseline, risk association of family history of late-onset diabetes with incident diabetes was not sustained, whereas that of family history of young-onset diabetes remained robust on further adjustment for baseline glycaemic measurements. CONCLUSIONS: First-degree relatives of people with Type 2 diabetes, especially relatives of those with young-onset diabetes, are at high risk for diabetes.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Evaluation of erectile dysfunction and associated cardiovascular risk using structured questionnaires in Chinese type 2 diabetic men.

Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type 2 diabetic men. In this study, we aimed to explore the frequency and severity of ED in Chinese type 2 diabetic men using a structured questionnaire. We furthermore sought to investigate the associations of ED with diabetes-related complications and metabolic indices. A consecutive cohort of 313 Chinese type 2 diabetic men aged between 25 and 76 years attending a diabetic centre were recruited between October 2006 and June 2007. Of the study population, the frequency of ED was 39.3% according to the National Institutes of Health (NIH) Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5) questionnaire. After adjusting for potential confounding factors by multivariable logistic regression, ED defined by NIH criterion was associated with advanced age [OR = 1.05 (95% CI 1.01-1.09), p = 0.012], the presence of diabetic retinopathy [OR = 2.43 (95% CI 1.27-4.66), p = 0.008] and coronary heart disease [OR = 2.63 (95% CI 1.21-5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced age [OR = 1.12 (95% CI 1.06-1.17), p < 0.0001], use of insulin therapy [OR = 2.94 (95% CI 1.12-7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29 (95% CI 1.05-5.01), p = 0.037]. In conclusion, ED was highly prevalent in Chinese type 2 diabetic men and was associated with multiple cardiovascular risk factors and complications. Advanced age, use of insulin therapy, the existence of microvascular complications such as retinopathy, albuminuria and coronary heart disease were associated with ED. NIH criteria diagnosed a much lower rate of ED compared with IIEF-5. Overall, structured questionnaires are useful and objective tools to detect ED, which should prompt a comprehensive risk assessment in these subjects.

Cast nephropathy with acute renal failure treated with high cut-off haemodialysis in a patient with multiple myeloma.

We report a case of a Chinese woman who presented with multiple myeloma and acute renal failure due to cast nephropathy, with an extremely high serum lambda free light chain concentration. She was successfully treated with chemotherapy and high cut-off extended haemodialysis. High cut-off haemodialysis is a new treatment modality which can achieve rapid free light chain clearance. This may contribute to a better renal outcome and overall prognosis for patients with multiple myeloma.

Cardiovascular risks and metabolic syndrome in Hong Kong Chinese women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS). METHODS: A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia. RESULTS: Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS. CONCLUSIONS: There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

The NCEP-ATPIII but not the IDF criteria for the metabolic syndrome identify Type 2 diabetic patients at increased risk of chronic kidney disease.

AIM: To examine the association between chronic kidney disease (CKD) and the metabolic syndrome (MetS) using both International Diabetes Federation (IDF) and National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATPIII) definitions in Chinese subjects with Type 2 diabetes. METHODS: Subjects with Type 2 diabetes were categorized according to the presence or absence of MetS by IDF or NCEP-ATPIII criteria. CKD was considered present if glomerular filtration rate, calculated using the abbreviated equation developed by the Modification of Diet in Renal Disease study with Chinese modification, was < 60 ml/min per 1.73 m2. Multivariate logistic regression analysis of the association between CKD and MetS by either definition was performed. RESULTS: Of 6350 subjects (mean age 55.1 +/- 13.3 years), 3439 (54.2%) and 3204 (50.5%) had MetS by IDF and NCEP-ATPIII definitions, respectively. Using the IDF definition, the presence of MetS was not associated with CKD [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.71, 1.29, P = 0.784]. In contrast, the association with CKD was significant when MetS was defined by the NCEP-ATPIII definition (OR 1.75, 95% CI 1.37, 2.24, P < 0.001). In subjects who did not have MetS (n = 2911) as defined by IDF criteria, 997 fulfilled the MetS criteria of NCEP-ATP III. The association with CKD was stronger, after adjustment for covariates, in these subjects (OR 1.42, 95% CI 1.03, 1.97, P = 0.032) compared with subjects who met IDF criteria of MetS. CONCLUSION: In Type 2 diabetes, NCEP-ATPIII, but not the IDF definition of MetS, identifies a subgroup of patients who have a higher risk of CKD.

A novel CASR gene mutation in an octogenarian with asymptomatic hypercalcaemia.

An increasing number of patients are diagnosed with primary hyperparathyroidism after having hypercalcaemia detected incidentally during routine biochemical screening. Many are asymptomatic at the time of diagnosis. An 80-year-old woman was found to have asymptomatic hypercalcaemia. Initial investigations suggested a diagnosis of primary hyperparathyroidism. Subsequent investigations revealed that, in fact, she had familial hypocalciuric hypercalcaemia. Direct DNA sequencing of the calcium-sensing receptor (CASR) gene confirmed that the patient was heterozygous for c.2501delC, a novel frame shift mutation predicted to cause loss of function of the CASR gene. Several other family members were subsequently found to carry the same mutation. Suspected cases of hypocalciuric hypercalcaemia should be confirmed by detection of mutations within the CASR gene. Establishing the correct diagnosis will enable the patient and family members to avoid unnecessary investigations or operations.

A Chinese family with familial paraganglioma syndrome due to succinate dehydrogenase deficiency.

We report the genetic characteristics of a family with familial paraganglioma syndrome. The index patient was diagnosed with carcinoid tumour of the bronchus at the age of 30 years then later diagnosed with bilateral phaeochromocytoma. His sister had bilateral carotid body tumours. Mutational analyses of succinate dehydrogenase B and SDHD on the index patient showed him to be heterozygous for the M1I mutation of the SDHD gene. A genetic analysis revealed that his sister also had succinate dehydrogenase deficiency with the same mutation. Pre-symptomatic testing confirmed the genetic diagnosis, and led to a clinical diagnosis in an otherwise asymptomatic sibling. Comparison with other known cases of M1I mutation suggests that this is a founder mutation in the Chinese population. Genetic analysis of the succinate dehydrogenase genes can provide a specific diagnosis and allow for genetic screening of at-risk individuals.

Metabolic syndrome by the international diabetes federation definition in Hong Kong Chinese.

In this report, we aimed to examine the impact of the new International Diabetes Federation (IDF) definition on the prevalence and clinical characteristics of subjects with metabolic syndrome (MES). Data were obtained from a prevalence survey for cardiovascular risk factors in a Hong Kong Chinese working population. There were 1513 subjects well representing all occupational groups from managers to general laborers [910 (60.1%) men and 603 (39.9%) women (mean age 37.5+/-9.2, median 37.0, range 18-66 years)]. The crude prevalence of MES defined by the IDF criterion was 7.4% (compared to other criteria: NCEP, 9.6%; WHO, 13.4% and EGIR, 8.9%). The age-standardized prevalence of MES by the IDF criterion was 8.8% in women and 7.3% in men. Subjects with MES defined by IDF criterion had higher body mass index and waist compared to those with MES defined by NCEP or WHO criteria, and lower triglyceride compared to those with MES defined by NCEP criterion after adjustment for age, gender and smoking. Non-MES subjects defined by IDF criterion had higher 2h glucose and insulin resistance compared to non-MES subjects defined by WHO. In conclusion, the new IDF criterion for MES is easy to implement in clinical practice. It may be potentially more 'specific' in identifying subjects with MES although compared to the NCEP criterion, it may have missed a proportion of subjects, especially men, who have metabolic derangement. Prospective and interventional studies are needed to validate the prognostic values of this new definition in comparison with other existing definitions.

Fatal hepatitis associated with ketoconazole therapy.

A 67-year-old woman receiving ketoconazole, 200 mg daily for two months, had progressive jaundice, anorexia, and malaise develop. She had greatly elevated liver enzyme levels on hospital admission, and she died as a result of rapidly progressive liver failure. Histologic findings at autopsy disclosed acute hepatic necrosis. There was no clinical or serologic evidence of viral hepatitis. It is suggested that ketoconazole therapy was a causal factor in this case of fatal hepatic failure.

Polycystic ovarian syndrome in Hong Kong Chinese women: patient characteristics and diagnostic criteria.

OBJECTIVES: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria. DESIGN: Retrospective study. SETTING: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong. PATIENTS: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria. MAIN OUTCOME MEASURES: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance. RESULTS: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests. CONCLUSIONS: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients.

OBJECTIVES: Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs). RESEARCH DESIGN AND METHODS: Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization. RESULTS: Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group. CONCLUSIONS: In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement.

Outcomes of screening for diabetes in high-risk Hong Kong Chinese subjects.

OBJECTIVE: To examine the significance of individual risk factors on the development of diabetes in subjects who underwent screening for diabetes. RESEARCH DESIGN AND METHODS: A total of 1,649 Chinese subjects underwent screening for diabetes. They were asymptomatic but had known risk factors for diabetes, including a positive family history of diabetes, a past history of gestational diabetes, obesity, hypertension, and/or dyslipidemia. Another 799 age-matched subjects from the community who had no risk factors for diabetes were used as the comparison group. RESULTS: Of the 1,649 subjects who underwent screening, 241 (14.6%) had diabetes. In these subjects, 989 (60.0%) had 1 risk factor, 502 (30.4%) had 2 risk factors, 141 (8.6%) had 3 risk factors, and 17 (1.0%) had 4 or 5 risk factors for diabetes. Of the 799 control subjects, 29 (3.6%) had diabetes. Compared with the comparison group, the odds ratio (95% CI) of having diabetes after adjustment for age was 5.2 (3.5-7.7) in the 1,649 subjects with known risk factors. The odds ratio of having diabetes increased from 3.7 in subjects with 1 risk factor to 28.4 in subjects with 4 or 5 risk factors. CONCLUSIONS: In men, age, BMI, family history of diabetes, and dyslipidemia, and in women, age, BMI, hypertension, dyslipidemia, total cholesterol, and history of gestational diabetes are associated with increased odds of developing diabetes. These risk factors have additive effects on the odds of having diabetes. Early and regular screening for diabetes and other cardiovascular risk factors is essential in these high-risk individuals.

Dexfenfluramine in obese Chinese NIDDM patients. A placebo-controlled investigation of the effects on body weight, glycemic control, and cardiovascular risk factors.

OBJECTIVE: To investigate the safety, efficacy, and metabolic effects of dexfenfluramine in obese Chinese NIDDM patients. RESEARCH DESIGN AND METHODS: Thirty-two patients, mean (+/- SD) body weight 76.2 +/- 8.5 kg with corresponding BMI 31.1 +/- 2.1 kg/m2, were randomized into a two-phase study, after a 2-week single-blind run-in period on placebo. Phase 1 was a randomized 3-month double-blind placebo-controlled trial during which either dexfenfluramine or placebo was added to the existing treatment regimens of diet plus or minus sulfonylureas without metformin. Phase 2 was a further 3-month single-blind trial during which the placebo group was given dexfenfluramine without patients' knowledge of changing to active medication, while the active group continued with dexfenfluramine. Body weight, glycemic control, blood pressure, lipids, and quality of life were assessed before and at 3 and 6 months after randomization. A total of 27 patients were also followed for an additional period of 6-12 months (215 +/- 53 days) after dexfenfluramine treatment was withdrawn. RESULTS: During the run-in period, both groups were comparable for all parameters measured. At 3 months, mean changes in BMI were -1.2 +/- 1.0 kg/m2 (dexfenfluramine) vs. -0.1 +/- 0.5 kg/m2 (placebo) (P < 0.001). The mean changes in fasting plasma glucose were -1.14 +/- 0.99 vs. 0.51 +/- 1.34 mmol/l (dexfenfluramine vs. placebo, P = 0.004). HbA(1c) also significantly improved in the dexfenfluramine group (-0.80 +/- 0.53 vs. 0.25 +/- 0.64%, P < 0.001). During the 3-month single-blind dexfenfluramine treatment in the ex-placebo group, there were similar improvements in body weight and glycemic indexes. After cessation of dexfenfluramine therapy at 6 months, significant increases in body weight and glycemic indexes, almost back to the baseline, were observed for both groups. CONCLUSIONS: Dexfenfluramine aids weight loss and improves glycemic control in obese Chinese NIDDM patients over a 3- to 6-month period. These effects are emphasized after withdrawal of treatment and further support the longer-term use of dexfenfluramine for chronic complicated obesity.

Factors predicting the age when type 2 diabetes is diagnosed in Hong Kong Chinese subjects.

OBJECTIVE: To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese. RESEARCH DESIGN AND METHODS: The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios. RESULTS: Approximately 29% of the index patients were diagnosed with type 2 diabetes at < or = 35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at >35 years of age (hereby defined as late-onset) the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P < 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal was well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted olderq age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes Predictors for younger age at diagnosis in the female patients were higher HbA1c WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child parent pairs and clild-parent-grandparent trios there was a decrease in age at diagnosis in successive generations. CONCLUSIONS: Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.

Plasma insulin, growth hormone, cortisol, and central obesity among young Chinese type 2 diabetic patients.

OBJECTIVE: To examine the relationships between central obesity, insulin resistance index, plasma insulin, growth hormone (GH), and cortisol concentrations in 90 young Chinese type 2 diabetic patients (aged 33+/-5 years) and 104 age- and sex-matched control subjects (aged 32+/-9 years). RESEARCH DESIGN AND METHODS: Young Chinese diabetic patients (aged <40 years) were recruited from the Prince of Wales Hospital. Blood pressure, height, weight, and waist and hip circumferences were determined. Venous blood was sampled for measurements of fasting plasma glucose, HbA1c, lipids, creatinine, insulin, GH, and cortisol. A 24-h urine was assayed for urinary albumin excretion (UAE). General and central obesity was represented by BMI and waist circumference, respectively. Insulin resistance index was estimated as a product of fasting plasma insulin and glucose concentrations. RESULTS: Compared with control subjects, diabetic patients were more obese, hyperglycemic, and had worse lipid profile, higher blood pressures, UAE, insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.001) but lower GH concentrations (P < 0.05). When analyzed as a whole group (n = 194), increasing quartiles of waist circumference were associated with increasing trends of insulin resistance index, plasma insulin, and cortisol concentrations (all P < 0.01) but a decreasing trend of plasma GH concentration (P < 0.05). Using stepwise multiple regression analysis, waist circumference was only associated with sex variable (being higher in men) in the control subjects. In the diabetic group, 51% of waist circumference was independently related to male sex and increased plasma insulin and cortisol concentrations as well as reduced plasma GH levels. CONCLUSIONS: In young Chinese type 2 diabetic patients, hyperinsulinemia, hypercortisolemia, and reduced plasma GH levels were closely associated with central obesity. Based on these findings, we postulate that maladaptive hormonal responses to rapid changes in lifestyle may have led to obesity and type 2 diabetes in these young patients. Alternatively, lifestyle-related obesity may have given rise to these hormonal changes. More studies are required to delineate the nature of these relationships.