Consensus Statements from the Diabetologists & Endocrinologists Alliance for the Management of People with Hypertension and Type 2 Diabetes Mellitus.

Hypertension and type 2 diabetes mellitus (T2DM) are important, intertwined public health issues. People with both conditions face significantly elevated risks of cardiovascular (CV) and renal complications. To optimize patient care, a multidisciplinary expert panel met to review recent evidence on optimal blood pressure (BP) targets, implications of albuminuria, and treatment regimens for hypertensive patients with T2DM, with the aim of providing recommendations for physicians in Hong Kong. The panel reviewed the relevant literature, obtained by searching PubMed for the publication period from January 2015 to June 2021, to address five discussion areas: (i) BP targets based on CV/renal benefits; (ii) management of isolated systolic or diastolic hypertension; (iii) roles of angiotensin II receptor blockers; (iv) implications of albuminuria for CV/renal events and treatment choices; and (v) roles and tools of screening for microalbuminuria. The panel held three virtual meetings using a modified Delphi method to address the discussion areas. After each meeting, consensus statements were derived and anonymously voted on by every panelist. A total of 17 consensus statements were formulated based on recent evidence and expert insights regarding cardioprotection and renoprotection for hypertensive patients with T2DM.

Clinical use of sodium-glucose co-transporter-2 inhibitors in Chinese patients with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM), the tenth leading cause of death in Hong Kong, has a prevalence of approximately 10%. Sodium-glucose co-transporter-2 (SGLT2) inhibitors lower glycated haemoglobin (HbA1c) levels in T2DM patients via a non-insulin-dependent mechanism of action, but real-world data is limited, particularly for Chinese patients. METHODS: A retrospective single-centre study was performed among Chinese patients with T2DM who were prescribed SGLT2 inhibitor therapy in Hong Kong. Changes in HbA1c levels, body weight, systolic and diastolic blood pressure, estimated glomerular filtration rate (eGFR), lipid profiles and adverse events were observed for patients who completed at least one follow-up visit during the study period. RESULTS: Overall, 100 patients were included, and 53 patients attended an additional final visit. By the final visit, SGLT2 inhibitor therapy had significantly decreased HbA1c levels (change [Δ] 0.31%, 95% confidence interval [CI] -0.11% to -0.51%, p < 0.001), body weight (Δ -4.59 kg, 95% CI -3.75 to -5.54 kg, p < 0.001) and systolic blood pressure (Δ -5.72 mmHg, 95% CI -1.72 to -9.72 mmHg, p < 0.001) from baseline. No significant change in eGFR or lipid profiles was observed, except for a significant reduction in high-density lipoprotein cholesterol (Δ -0.09 mmol/L, 95% CI -0.16 to -0.02 mmol/L, p < 0.05). Adverse events were consistent with previous reports for SGLT2 inhibitors, apart from appetite loss associated with canagliflozin. CONCLUSION: The real-world efficacy and safety profile of SGLT2 inhibitors in Chinese patients was comparable to that reported in Phase III clinical trials, with the exception of appetite loss among patients who received canagliflozin.

Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience.

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.

Metabolic profiles and treatment gaps in young-onset type 2 diabetes in Asia (the JADE programme): a cross-sectional study of a prospective cohort.

BACKGROUND: The prevalence of diabetes is increasing in young adults in Asia, but little is known about metabolic control or the burden of associated complications in this population. We assessed the prevalence of young-onset versus late-onset type 2 diabetes, and associated risk factors and complication burdens, in the Joint Asia Diabetes Evaluation (JADE) cohort. METHODS: JADE is an ongoing prospective cohort study. We enrolled adults with type 2 diabetes from 245 outpatient clinics in nine Asian countries or regions. We classified patients as having young-onset diabetes if they were diagnosed before the age of 40 years, and as having late-onset diabetes if they were diagnosed at 40 years or older. Data for participants' first JADE assessment was extracted for cross-sectional analysis. We compared clinical characteristics, metabolic risk factors, and the prevalence of complications between participants with young-onset diabetes and late-onset diabetes. FINDINGS: Between Nov 1, 2007, and Dec 21, 2012, we enrolled 41,029 patients (15,341 from Hong Kong, 9107 from India, 7712 from Philippines, 5646 from China, 1751 from South Korea, 705 from Vietnam, 385 from Singapore, 275 from Thailand, 107 from Taiwan). 7481 patients (18%) had young-onset diabetes, with age at diagnosis of mean 32·9 years [SD 5·7] versus 53·9 years [9·0] with late-onset diabetes (n=33,548). Those with young-onset diabetes had longer disease duration (median 10 years [IQR 3-18]) than those with late-onset diabetes (5 years [2-11]). Fewer patients with young-onset diabetes achieved HbA1c concentrations lower than 7% compared to those with late-onset diabetes (27% vs 42%; p<0·0001) Patients with young-onset diabetes had higher mean concentrations of HbA1c (mean 8·32% [SD 2·03] vs 7·69% [1·82]; p<0·0001), LDL cholesterol (2·78 mmol/L [0·96] vs 2·74 [0·93]; p=0·009), and a higher prevalence of retinopathy (1363 [20%] vs 5714 (18%); p=0·011) than those with late-onset diabetes, but were less likely to receive statins (2347 [31%] vs 12,441 [37%]; p<0·0001) and renin-angiotensin-system inhibitors (1868 [25%] vs 9665 [29%]; p=0·006). INTERPRETATION: In clinic-based settings across Asia, one in five adult patients had young-onset diabetes. Compared with patients with late-onset diabetes, metabolic control in those with young-onset diabetes was poor, and fewer received organ-protective drugs. Given the risk conferred by long-term suboptimum metabolic control, our findings suggest an impending epidemic of young-onset diabetic complications. FUNDING: The Asia Diabetes Foundation (ADF) and Merck.

Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

BACKGROUND: A recently halted clinical trial showed that intensive treatment of type 2 diabetes mellitus was associated with increased mortality. Given the phenotypic heterogeneity of diabetes, therapy targeted at insulin status may maximize benefits and minimize harm. METHODS: In this longitudinal cohort study, we followed 503 patients with type 2 diabetes who were free of cardiovascular disease from 1996 until data on mortality and cardiovascular outcomes were censored in 2005. Phenotype-targeted therapy was defined as use of insulin therapy in patients with a fasting plasma C peptide level of 0.2 nmol/L or less and no insulin therapy in patients with higher C peptide levels. RESULTS: The mean age of the cohort was 54.4 (standard deviation 13.1) years, and 56% were women. The mean duration of diabetes was 4.6 years (range 0-35.9 years). Of the 503 patients, 110 (21.9%) had a low C peptide level and 111 (22.1%) were given insulin. Based on their C peptide status, 338 patients (67.2%) received phenotype-targeted therapy (non-insulin-treated, high C peptide level [n = 310] or insulin-treated, low C peptide level [n = 28]), and 165 patients (32.8%) received non-phenotype-targeted therapy (non-insulin-treated, low C peptide level [n = 82] or insulin-treated, high C peptide level [n = 83]). Compared with the insulin-treated, low-C-peptide referent group, the insulin-treated, high-C-peptide group was at a significantly higher risk of cardiovascular events (hazard ratio [HR] 2.85, p = 0.049) and death (HR 3.43, p = 0.043); the risk was not significantly higher in the other 2 groups. These differences were no longer significant after adjusting for age, sex and diabetes duration. INTERPRETATION: Patients with low C peptide levels who received insulin had the best clinical outcomes. Patients with normal to high C peptide levels who received insulin had the worst clinical outcomes. The results suggest that phenotype-targeted insulin therapy may be important in treating diabetes.

Effects of treatment targets on subsequent cardiovascular events in Chinese patients with type 2 diabetes.

OBJECTIVE: International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C <7.0%, blood pressure <130/80 mmHg, and LDL cholesterol <2.6 mmol/l. RESULTS: After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% CI 0.50-0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin. CONCLUSIONS: Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes.

Treatment-related stresses and anxiety-depressive symptoms among Chinese outpatients with type 2 diabetes mellitus in Hong Kong.

Based on focus group findings, a descriptive instrument was developed to examine the relationship among treatment-related stress, anxiety and depressive symptoms, distress, and impairment of 333 Chinese outpatients with type 2 diabetes mellitus (DM) in Hong Kong. It was found that the main stresses included fears of diabetes complications, work impairment, lifestyle adjustment, stigmatization, and discrimination. Over 1/4 of patients concealed their DM from family members in order not to make the latter worry. 28.3% felt that life was not worth living. 33.6% of patients exhibited four or more anxiety and depressive symptoms accompanied by significant distress and/or impairment. These patients were more likely to be female, of lower educational level, and unemployed. Diabetes complications, concealment of DM, and feeling of being a burden to the family predicted anxious-depressed status. The study showed that treatment-related stresses and anxiety-depressive symptoms were common and associated among Chinese diabetes outpatients in Hong Kong.

Mesenteric fat thickness is an independent determinant of metabolic syndrome and identifies subjects with increased carotid intima-media thickness.

OBJECTIVE: Mesenteric fat, a reflection of visceral adiposity, may play an important role in the pathogenesis of metabolic syndrome and cardiovascular diseases (CVD). In this study, we examined the independent relationship between mesenteric fat thickness and metabolic syndrome and defined its optimal cutoff value to identify high-risk subjects for metabolic syndrome and CVD. RESEARCH DESIGN AND METHODS: A total of 290 Chinese subjects had an ultrasound examination for measurements of thickness of mesenteric, preperitoneal, and subcutaneous fat as well as carotid intima-media thickness (IMT). Anthropometric measurements and metabolic risk profile were assessed by physical examination and blood taking. RESULTS: Twenty (6.9%) subjects had metabolic syndrome according to the National Cholesterol Education Panel Adult Treatment Panel III criteria with Asian definitions for central obesity (waist circumference >80 cm in women and >90 cm in men). Mesenteric fat thickness had significant correlations (P < 0.05) with various metabolic variables. On multivariate regression, mesenteric fat thickness was an independent determinant of all components of metabolic syndrome after adjustment for age, sex, homeostasis model assessment of insulin resistance, and other fat deposits. The odds ratio of metabolic syndrome was increased by 1.35 (95% CI 1.10-1.66)-fold for every 1-mm increase in mesenteric fat thickness. On receiver-operating characteristic curve analysis, mesenteric fat thickness of > or =10 mm was the optimal cutoff value to identify metabolic syndrome, with sensitivity of 70% and specificity of 75%. Subjects with mesenteric fat thickness > or =10 mm had higher carotid IMT than those with thickness <10 mm (0.73 +/- 0.19 vs. 0.64 +/- 0.16 mm, P = 0.001). CONCLUSIONS: Mesenteric fat thickness was an independent determinant of metabolic syndrome and identified subjects with increased carotid IMT.

High prevalence of metabolic syndrome in Hong Kong Chinese--comparison of three diagnostic criteria.

The World Health Organisation (WHO), European Group for the Study of Insulin Resistance (EGIR) and National Cholesterol Education Program (NCEP) Expert Panels had introduced definitions for the metabolic syndrome (MES). We aimed to estimate the prevalence of MES in a working population in Hong Kong using the three definitions for MES and compare their relative significance. The data are obtained from a prevalence survey for glucose intolerance and lipid abnormality in a Hong Kong Chinese working population. The distribution of occupational groups in these subjects was similar to that recorded in the Hong Kong Census (1991) and representative of the Hong Kong working population. Definition of obesity was modified using the Asian criterion of body mass index (BMI)> or =25 kg/m 2, waist circumference>80 cm in women and >90 cm in men. Of the 1513 subjects, 910 (60.1%) were men and 603 (39.9%) were women. The mean age was 37.5+/-9.2 (median 37.0 years, range 18-66 years). Using the Asian definition for obesity, the prevalence of MES using the WHO criterion was the highest (WHO versus EGIR versus NCEP-overall: 13.4% versus 8.9% versus 9.6%, p<0.001; under age of 40 years: 7.9% versus 4.9% versus 5.4%, p=0.017; age of 40 years or above: 21.9% versus 14.9% versus 16.0%, p=0.003). The prevalence of different components of the MES ranged from 6 to 38%. In subjects aged less than 50 years, there was a male preponderance for MES (male versus female-WHO: 9.5% versus 6.2%, p=0.007; EGIR: 7.9% versus 6.2%, p=0.235; NCEP: 9.5% versus 6.2%, p=0.030) but this trend was reversed after the age of 50 years (WHO: 29.3% versus 31.9%, p=0.721; EGIR: 13.1% versus 34.8%, p=0.001; NCEP: 19.2% versus 23.2%, p=0.533). The prevalence of MES in Hong Kong Chinese of working age ranges from 6.1 to 13.4% depending on various diagnostic criteria. There was a male preponderance before the age of 50 years and a female-preponderance after the age of 50 years. The inclusion of albuminuria and insulin resistance by the WHO has made it the most discriminative criterion in identifying at risk individuals in all age groups.

Effects of body mass index, plasma glucose and cholesterol levels on isolated systolic hypertension.

Despite the high cardiovascular risk of diabetic patients, there is a paucity of data on isolated systolic hypertension (ISH) in diabetic patients. In this cross-sectional study, we examined the risk of ISH and its associated factors in Chinese type 2 diabetic patients. Isolated systolic hypertension was defined as systolic blood pressure (SBP) > or =140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg. The mean value of two BP measurements taken 1 min apart was used. There were 1048 type 2 diabetic patients recruited from the Prince of Wales Hospital Diabetes Clinic. Another 1043 age- and sex-matched non-diabetic subjects were recruited from the community. The mean age of the 2091 subjects was 40.6 +/- 7.6 years (median: 40 years, range: 16-69 years). Diabetic patients had an increased risk of ISH compared to non-diabetic subjects (7.6% vs. 3.4%, p < 0.001) with an odd ratio of 2.38. On multivariate analysis, age, body mass index, total cholesterol and duration of diabetes in diabetic subjects while age and waist-hip ratio (WHR) in non-diabetic subjects were independently associated with ISH. In conclusion, Chinese type 2 diabetic patients had increased risk to develop ISH than non-diabetic subjects. Age, obesity, lipid and duration of diabetes were independent associated with ISH. These findings suggest that control of body weight and metabolic profile might have beneficial effects on ISH.

Cyanosis in a compulsive urine drinker.

An 18-year-old gentleman with a habit of compulsive urine drinking was admitted because of repeated vomiting and was noted to be cyanotic. His oxygen saturation was 84% on pulse oximeter but arterial blood gas was normal. He was subsequently confirmed to have methemoglobinemia. He was successfully treated with methylene blue followed by behavioral therapy for his compulsive urine drinking and there was no recurrence of methaemoglobinaemia.

The renoprotective effects of structured care in a clinical trial setting in type 2 diabetic patients with nephropathy.

BACKGROUND: The RENAAL Study has confirmed the renoprotective effects of Losartan in type 2 diabetes. In this subgroup analysis from the RENAAL Study, we hypothesized that the intensive care received by patients in a clinical trial setting also reduced the rate of decline in renal function through optimization of all risk factors. METHODS: We compared the rate of deterioration in renal function, expressed as the regression coefficient of the monthly serum creatinine (SeCr) reciprocal (beta-1/Cr) in 55 Chinese type 2 diabetic patients before and after entry into the RENAAL Study. RESULTS: Of the 55 patients, 44 had at least three out-patient SeCr measurements both before (2.9+/-2.4 years) and after (3.3+/-0.8 years) entry into the study for evaluation. In the Losartan group (n = 24), the median beta-1/Cr fell from -11.4 x 10(-5) l micro mol(-1) month(-1) before entry into the trial to -4.7 x 10(-5) l micro mol(-1) month(-1) following entry (P = 0.001). The respective figures were -9.1 x 10(-5) and -5.0 x 10(-5) l micro mol(-1) month(-1) (P = 0.01) in the placebo group (n = 20). A decrease in beta-1/Cr was observed in 21 (87.5%) and 14 (70.0%) patients in the Losartan and placebo groups, respectively. Spot urinary albumin-to-creatinine ratio was reduced by 56% (P = 0.001) in the Losartan group but the change was not significant in the placebo group. At the end of the study, patients in both groups had lower blood pressure and better lipid control. The frequency of patient visits to doctors and nurses were doubled. CONCLUSIONS: The rate of renal function decline was significantly reduced in the majority of patients allocated to either Losartan or placebo following entry into the RENAAL study. These results suggest that in patients with diabetic nephropathy, implementation of a structured care protocol in a clinical trial setting facilities intensive treatment of risk factors confering renoprotective effects in addition to those resulting from Losartan treatment.

Effect of angiotensin-converting enzyme inhibition on survival in 3773 Chinese type 2 diabetic patients.

We assessed the effects of angiotensin-converting enzyme (ACE) inhibition on survival and cardiorenal outcomes in a consecutive cohort of Chinese type 2 diabetic patients with varying degree of albuminuria, ranging from normoalbuminuria to macroalbuminuria. A total of 3773 consecutive Chinese type 2 diabetic patients were followed prospectively for a mean period of 35.8 months. Clinical end points included all-cause mortality, with cardiovascular end point defined as first hospitalization because of ischemic heart disease, congestive heart failure, revascularization procedures, or cerebrovascular accident as well as renal end point defined as dialysis, doubling of baseline plasma creatinine, or plasma creatinine > or =500 micromol/L. The use of ACE inhibitor was 26.3% in normoalbuminuric (NA), 70.1% in microalbuminuric (MI), and 82.6% in macroalbuminuric (MA) groups. Albuminuria was a major predictor for all-cause mortality with 4-fold difference between NA and MA patients. The 7-year cumulative mortality rate was 7.1%, 10.8%, and 21.7% in the NA, MI, and MA groups, respectively. The use of ACE inhibition was associated with significant reduction of mortality (hazard ratio 0.41 and 95% confidence interval, 0.29, 0.58) in the entire group and was most evident in high-risk patients who had cardiorenal complications or retinopathy at baseline for all albuminuric groups (NA 0.76 [0.31,1.87]; MI 0.32 [0.16, 0.65]; and MA 0.20 [0.13, 0.33]). The prognostic value of albuminuria for death in type 2 diabetes and the beneficial effects of ACE inhibitors in Chinese type 2 diabetic patients with micro- or macroalbuminuria has been confirmed. The effects of ACE inhibitors in type 2 diabetic patients with normoalbuminuria require further evaluation.

Effects of obesity on the conversion from normal glucose tolerance to diabetes in Hong Kong Chinese.

OBJECTIVE: To assess the effects of BMI on progression to diabetes in Hong Kong Chinese and to analyze the optimal cutoff for overweight and obesity in Hong Kong Chinese. RESEARCH METHODS AND PROCEDURES: This is a prospective study with a mean follow-up of 2.1 years (median 1.4 years, range 0.9 to 8.4 years). We recruited 172 nondiabetic high-risk subjects, of whom 115 had normal glucose tolerance (NGT) and 57 had impaired glucose tolerance (IGT). BMI and 75-gram oral glucose tolerance tests were assessed at baseline and then at yearly intervals. RESULTS: The crude rates of progression to diabetes for subjects with NGT or IGT were 8.4% and 11.5% per year, respectively. For subjects with NGT, the progression rate to diabetes differed with different BMI ranges. For subjects with NGT and BMI > or = 25 kg/m2, the crude rates of progression to diabetes or glucose intolerance (diabetes or IGT) were 12.5% per year and 14.6% per year, respectively. The corresponding rates for subjects with NGT and BMI > or = 28 kg/m2 were 14.6% and 18.9% per year, respectively. Among subjects with NGT, those with BMI between 25 and 28 kg/m2 had the highest Youden index and likelihood ratio to predict the conversion to diabetes or glucose intolerance. DISCUSSION: Obese subjects with NGT had higher rates of progression to diabetes than nonobese subjects. We recommend redefining BMI cutoffs, with 23 kg/m2 for overweight and 28 kg/m2 for obesity. This definition may be more sensitive to identify at-risk subjects and more specific to identify "patients" for therapeutic management.

White blood cell count is associated with macro- and microvascular complications in chinese patients with type 2 diabetes.

OBJECTIVES: There are close associations among raised white blood cell (WBC) count, coronary heart disease, and metabolic syndrome in the general population. The association between WBC count and vascular complications of diabetes has not been explored. We carried out a cross-sectional cohort study to determine the association between WBC count and the presence of macro- and microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS: In this study, 3,776 patients with type 2 diabetes and normal WBC count (3.5-12.5 x 10(9)/l) underwent a comprehensive assessment of complications and cardiovascular risk factors based on the European DiabCare protocol. Demographic and anthropometric parameters were recorded. Metabolic profiles, including complete blood picture and urinary albumin excretion, were measured. RESULTS: Patients with higher WBC counts (categorized into quintiles) had adverse metabolic profiles as evidenced by higher blood pressure, BMI, HbA(1c), fasting plasma glucose, LDL cholesterol, triglycerides, and urinary albumin excretion, but lower HDL cholesterol (all P <0.001 for trend). The prevalence of macro- and microvascular complications increased in a dosage-related manner with WBC count. After adjustments for smoking and other known cardiovascular risk factors, a 1-unit (1 x 10(9)/l) increment of WBC count was associated with a 15.8% (95% CI 9.3-22.6; P < 0.001) and 12.3% increase (5.8-19.1; P < 0.001) in the prevalence of macro- and microvascular complications, respectively. CONCLUSIONS: Elevated WBC count, even within the normal range, is associated with both macro- and microvascular complications in type 2 diabetes. Chronic inflammation, as indicated by a higher WBC count, may play a linkage role in the development of macro- and microvascular complications in diabetes.

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.