What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts.

OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary heart disease. We sought to determine ethnic differences in newborn adiposity comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two birth cohorts in Canada were analyzed. Pregnant women completed a health assessment including a 75-g oral glucose tolerance test to assess for dysglycemia. Birthweight, length, waist and hip circumference, and triceps and subscapular skinfold thickness (a surrogate measure of body adiposity) were measured in all newborns. Multivariate regression was used to identify maternal factors associated with newborn skinfold measurements. RESULTS: South Asian women were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns, South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn skinfold thickness included South Asian ethnicity (standardized estimate (s.e.): 0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight and have greater skinfold thickness, compared with White newborns, and this is influenced by maternal body fat and glucose. Interventions aimed at reducing body fat prior to pregnancy and gestational diabetes during pregnancy in South Asians may favorably alter newborn body composition and require evaluation.

Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial.

AIMS: Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance. METHODS: After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed. RESULTS: Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 µg/ml with rosiglitazone and by 0.4 µg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids. CONCLUSIONS: In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.

Increased cardiovascular risk after pre-eclampsia in women with dysglycaemia.

AIMS: Compared with women with uncomplicated pregnancies, women with a history of pre-eclampsia have two to five times the risk of cardiovascular disease. It is not known whether this risk is related to albuminuria, a known cardiovascular risk factor that is part of the definition of pre-eclampsia and that often persists after delivery. Our objective was to determine if the high risk of cardiovascular disease in women with pre-eclampsia is accounted for by known cardiovascular risk factors including albuminuria. METHODS: We performed a cross-sectional analysis of 4080 dysglycaemic women enrolled in a large randomized controlled trial who provided an obstetric history and had at least one delivery. Blood pressure, height, weight, waist circumference and hip circumference were measured. An oral glucose tolerance test, lipids, an electrocardiogram and an albumin/creatinine ratio from a first morning urine sample were obtained. RESULTS: There were 3613 women with no history of pre-eclampsia during their pregnancies, 108 with severe pre-eclampsia and 359 with non-severe pre-eclampsia. Women with a history of severe pre-eclampsia had higher rates of previous cardiovascular disease than women with non-severe pre-eclampsia or women without pre-eclampsia (87, 72 and 72%, P = 0.0019). The high risk of previous cardiovascular disease in women with a history of severe pre-eclampsia (odds ratio 2.67, 95% CI 1.52-4.70) persisted after adjustment for albuminuria (odds ratio 2.74, 95% CI 1.55-4.83) and also after adjusting for other covariates including albuminuria (odds ratio 3.03, 95% CI 1.69-5.44). CONCLUSION: Even after accounting for cardiovascular risk factors including albuminuria, a history of severe pre-eclampsia is independently associated with a threefold higher risk of cardiovascular disease.

Design, history and results of the Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) randomised controlled trial.

AIMS/OBJECTIVE: Conflicting data regarding cardiovascular effects of thiazolidinediones (TZDs) and extra-skeletal effects of vitamin D supported the need for a definitive trial. The Thiazolidinedione Intervention with vitamin D Evaluation (TIDE) trial aimed to assess the effects of TZDs (rosiglitazone and pioglitazone) on cardiovascular outcomes and the effects of vitamin D (cholecalciferol) on cancers and mortality. METHODS: A large multicentre 3 × 2 factorial double-blind placebo-controlled randomised trial recruited from outpatient primary care and specialty clinics in 33 countries. From June 2009 to July 2010, 1,332 people with type 2 diabetes and other cardiovascular risk factors aged ≥ 50 years whose HbA(1c) was 6.5-9.5% (48-80 mmol/mol) when using two or fewer glucose-lowering drugs were randomised by a central computer system to placebo (n = 541), rosiglitazone 4-8 mg/day (n = 399) or pioglitazone 30-45 mg/day (n = 392); 1,221 participants were randomised to placebo (n = 614) or vitamin D 1,000 IU/day (n = 607). Participants and all study personnel were blind to treatment allocation. The primary outcome for the TZD arm was the composite of myocardial infarction, stroke or cardiovascular death, and for the vitamin D arm it was cancer or all-cause death. All randomised participants were included in the primary analysis. RESULTS: From the study design, 16,000 people were to be followed for approximately 5.5 years. However, the trial was stopped prematurely because of regulatory concerns after a mean of 162 days without consideration of the accrued data. In the TZD arm, the cardiovascular outcome occurred in five participants (0.9%) in the placebo groups and three participants (0.4%) in the TZD groups (two allocated to pioglitazone, one to rosiglitazone). In the vitamin D arm, the primary outcome occurred in three participants (0.5%) in the placebo group and in two participants (0.3%) receiving vitamin D. Adverse events were comparable in all groups. CONCLUSIONS/INTERPRETATION: Uncertainty persists regarding the clinically relevant risks and benefits of TZDs and vitamin D because of the early cancellation of this comprehensive trial.

Poor achievement of guidelines-recommended targets in type 2 diabetes: findings from a contemporary prospective cohort study.

AIMS: To prospectively evaluate diabetes management in the primary care setting and explore factors related to guideline-recommended triple target achievement [blood pressure (BP) ≤ 130/80 mmHg, A1C ≤ 7% and low-density lipoprotein (LDL)-cholesterol < 2.5 mmol/l]. METHODS: Baseline, 6 and 12 month data on clinical and laboratory parameters were measured in 3002 patients with type 2 diabetes enrolled as part of a prospective quality enhancement research initiative in Canada. A generalised estimating equation model was fitted to assess variables associated with triple target achievement. RESULTS: At baseline, 54%, 53% and 64% of patients, respectively, had BP, A1C and LDL-cholesterol at target; all three goals were met by 19% of patients. The percentage of individuals achieving these targets significantly increased during the study [60%, 57%, 76% and 26%, respectively, at the final visit, p < 0.0001 except for A1C, p = 0.27]. A much smaller proportion of patients had adequate control during the entire study period [30%, 39%, 53% and 7%, respectively]. In multivariable analysis, women, patients younger than 65 years and patients of Afro-Canadian origin were less likely to achieve the triple target. DISCUSSION: As part of a quality enhancement research initiative, we observed important improvements in the attainment of guidelines-recommended targets in patients with type 2 diabetes followed for a 12-month period in the primary care setting; however, many individuals still failed to achieve and especially maintain optimal goals for therapy, particularly the triple target. Results of the multivariable analysis reinforce the need to address barriers to improve diabetes care, particularly in more susceptible groups.

Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes.

AIMS/HYPOTHESIS: The Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication (DREAM) trial reported that 3 years of therapy with rosiglitazone reduced the primary outcome of diabetes or death by 60%. Here we investigated whether an effect on diabetes prevention persists more than 1.5 years after therapy has been discontinued. METHODS: The DREAM On passive follow-up study was conducted at 49 of the 191 DREAM sites. Consenting participants were invited to have a repeat OGTT 1-2 years after active therapy ended. A diagnosis of diabetes at that time was based on either a fasting or 2 h plasma glucose level of ≥7.0 mmol/l or ≥11.1 mmol/l, respectively, or a confirmed diagnosis by a non-study physician. Regression to normoglycaemia was defined as a fasting and 2 h plasma glucose level of <6.1 mmol/l and <7.8 mmol/l, respectively. RESULTS: After a median of 1.6 years after the end of the trial and 4.3 years after randomisation, rosiglitazone participants had a 39% lower incidence of the primary outcome (hazard ratio [HR] 0.61, 95% CI 0.53-0.70; p < 0.0001) and 17% more regression to normoglycaemia (95% CI 1.01-1.34; p = 0.034). When the analysis was restricted to the passive follow-up period, a similar incidence of both the primary outcome and regression was observed in people from both treatment groups (HR 1.00, 95% CI 0.81-1.24 and HR 1.14, 95% CI 0.97-1.32, respectively). Similar effects were noted when new diabetes was analysed separately from death. Ramipril did not have any significant long-term effect. CONCLUSIONS/INTERPRETATION: Time-limited exposure to rosiglitazone reduces the longer term incidence of diabetes by delaying but not reversing the underlying disease process.

Anthropometric measures and glucose levels in a large multi-ethnic cohort of individuals at risk of developing type 2 diabetes.

AIMS/HYPOTHESES: We determined: (1) which of BMI, waist circumference, hip circumference and WHR has the strongest association and explanatory power for newly diagnosed type 2 diabetes and glucose status; and (2) the impact of considering two measures simultaneously. We also explored variation in anthropometric associations by sex and ethnicity. METHODS: We performed cross-sectional analysis of 22,293 men and women who were from five ethnic groups and 21 countries, and at risk of developing type 2 diabetes. Standardised anthropometric associations with type 2 diabetes and AUC of glucose status from OGTT (AUC(OGTT)) were determined using multiple regression. Explanatory power was assessed using the c-statistic and adjusted r (2). RESULTS: An increase in BMI, waist circumference or WHR had similar positive associations with type 2 diabetes, AUC(OGTT) and explanatory power after adjustment for age, sex, smoking and ethnicity (p < 0.01). However, using BMI and WHR together resulted in greater explanatory power than with other models (p < 0.01). Associations were strongest when waist circumference and hip circumference were used together, a combination that had greater explanatory power than other models except for BMI and WHR together (p < 0.01). Results were directionally similar according to sex and ethnicity; however, significant variations in associations were observed among these subgroups. CONCLUSIONS/INTERPRETATION: The combination of BMI and WHR, or of waist circumference and hip circumference has the best explanatory power for type 2 diabetes and glucose status compared with a single anthropometric measure. Measurement of waist circumference and hip circumference is required to optimally identify people at risk of type 2 diabetes and people with elevated glucose levels.

Dysglycaemia and the risk of acute myocardial infarction in multiple ethnic groups: an analysis of 15,780 patients from the INTERHEART study.

AIMS/HYPOTHESIS: Although diabetes is an established risk factor for myocardial infarction (MI), disease control may vary. HbA(1c) is a reliable index of ambient glucose levels and may provide more information on MI risk than diabetes status. METHODS: The relationship between HbA(1c) levels in MI patients and controls who participated in the 52 country INTERHEART study was analysed. RESULTS: In 15,780 participants with a HbA(1c) value (1,993 of whom had diabetes), the mean (SD) levels for HbA(1c) were 6.15% (1.10) in the 6,761 MI patients and 5.85% (0.80) in the control participants. After adjustment for age, sex and nine major MI risk factors (including diabetes), higher HbA(1c) fifths above the lowest fifth (HbA(1c) <5.4%) were associated with progressively higher OR of MI, with OR for the highest HbA(1c) fifth (≥ 6.12%) being 1.55 (95% CI 1.37-1.75). When analysed as a continuous variable after adjustment for the same factors, every 1% higher HbA(1c) value was associated with 19% (95% CI 14-23) higher odds of MI, while every 0.5% higher HbA(1c) was associated with 9% higher odds of MI (95% CI 7-11). Concordant relationships were noted across subgroups, with a higher OR noted in younger people, patients without diabetes or hypertension, and those from some regions and ethnicities. CONCLUSIONS/INTERPRETATION: The HbA(1c) value provides more information on MI odds than self-reported diabetes status or many other established risk factors. Every 1% increment independently predicts a 19% higher odds of MI after accounting for other MI risk factors including diabetes.

Effects of ethnicity on diabetes incidence and prevention: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial.

AIMS: Risk of Type 2 diabetes varies by ethnicity, but whether ethnicity remains important among those who have impaired glucose tolerance or impaired fasting glucose is uncertain. Whether the effect of thiazolidinedione treatment on diabetes prevention in persons with non-diabetic dysglycaemia varies by ethnicity is also not known. We addressed these questions using data collected in the DREAM trial. METHODS: A 2-by-2 factorial double-blind randomized controlled trial to compare the effects of rosiglitazone and ramipril on the primary outcome of diabetes or death in persons meeting criteria for impaired glucose tolerance or impaired fasting glucose. The effect of these interventions by ethnicity was estimated using Cox regression analysis. RESULTS: Of 5269 adults, 2365 were randomly assigned to rosiglitzone and 2634 to placebo. South Asians showed a higher hazard for the primary outcome compared with Europeans (hazard ratio, 95% confidence interval 2.21, 1.41-3.47) adjusted for age, gender, BMI, waist-hip ratio and geographic region. A lesser increase in risk was seen in Black people (1.37, 1.04-1.81). A significant reduction in risk of the primary outcome with rosiglitazone treatment assignment was seen in all ethnic groups, but the treatment effect significantly differed by ethnicity (P=0.0242), with South Asians experiencing a smaller, and Latinos a larger preventive effect. CONCLUSIONS: Ethnicity is an important risk factor for Type 2 diabetes in dysglycaemic persons. All ethnic groups experienced a large significant reduction in diabetes risk because of rosiglitazone. The magnitude of this reduction differed by ethnicity. Given the post hoc nature of this analysis, further confirmation of these findings is needed.

Intensive glucose control and macrovascular outcomes in type 2 diabetes.

AIMS/HYPOTHESIS: Improved glucose control in type 2 diabetes is known to reduce the risk of microvascular events. There is, however, continuing uncertainty about its impact on macrovascular disease. The aim of these analyses was to generate more precise estimates of the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with type 2 diabetes. METHODS: A prospectively planned group-level meta-analysis in which characteristics of trials to be included, outcomes of interest, analyses and subgroup definitions were all pre-specified. RESULTS: A total of 27,049 participants and 2,370 major vascular events contributed to the meta-analyses. Allocation to more-intensive, compared with less-intensive, glucose control reduced the risk of major cardiovascular events by 9% (HR 0.91, 95% CI 0.84-0.99), primarily because of a 15% reduced risk of myocardial infarction (HR 0.85, 95% CI 0.76-0.94). Mortality was not decreased, with non-significant HRs of 1.04 for all-cause mortality (95% CI 0.90-1.20) and 1.10 for cardiovascular death (95% CI 0.84-1.42). Intensively treated participants had significantly more major hypoglycaemic events (HR 2.48, 95% CI 1.91-3.21). Exploratory subgroup analyses suggested the possibility of a differential effect for major cardiovascular events in participants with and without macrovascular disease (HR 1.00, 95% CI 0.89-1.13, vs HR 0.84, 95% CI 0.74-0.94, respectively; interaction p = 0.04). CONCLUSIONS/INTERPRETATION: Targeting more-intensive glucose lowering modestly reduced major macrovascular events and increased major hypoglycaemia over 4.4 years in persons with type 2 diabetes. The analyses suggest that glucose-lowering regimens should be tailored to the individual.

Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk of developing congestive heart failure (CHF). However, the relationships between glucose levels and CHF in people with or without a history of DM have not been well characterized. METHODS AND RESULTS: We evaluated the associations between fasting plasma glucose and risk of hospitalization for CHF during follow-up in patients at high cardiovascular risk and without CHF enrolled in a large-scale clinical trials program. Baseline fasting plasma glucose levels were assessed in 31,546 high-risk subjects with > or = 1 coronary, peripheral, or cerebrovascular disease or DM with end-organ damage who are participating in 2 ongoing parallel trials evaluating the effects of telmisartan, ramipril, or their combination (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]; n=25,620) and the effects of telmisartan against placebo in angiotensin-converting enzyme-intolerant patients (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease [TRANSCEND]; n=5926). Interim analyses blinded for randomized treatment were performed to compare baseline fasting plasma glucose with the adjusted CHF event rate at a mean follow-up of 886 days. Multivariable Cox regression models were performed, and associations were reported as hazard ratios and 95% confidence intervals. Among all subjects (mean age, 67 years; 69% men), of whom 11,708 (37%) had known DM and 1006 (3.2%) had newly diagnosed DM at baseline, 668 patients were hospitalized for CHF during follow-up. After adjustment for age and sex, a 1-mmol/L-higher fasting plasma glucose was associated with a 1.10-fold-increased risk of CHF hospitalization (95% confidence interval, 1.08 to 1.12; P<0.0001). The association persisted after adjustment for age, sex, smoking, previous myocardial infarction, hypertension, waist-to-hip ratio, creatinine, DM, and use of aspirin, beta-blockers, or statins (hazard ratio, 1.05; 95% confidence interval, 1.02 to 1.08; P<0.001). CONCLUSIONS: Fasting plasma glucose is an independent predictor of hospitalization for CHF in high-risk subjects. These data provide theoretical support for potential direct beneficial effects of glucose lowering in reducing the risk of CHF and suggests the need for specific studies targeted at this issue.

Rosiglitazone prevents diabetes by increasing beta-cell mass in an animal model of type 2 diabetes characterized by reduced beta-cell mass at birth.

AIM: Interventions that preserve or increase beta-cell mass may also prevent type 2 diabetes. Rosiglitazone prevents diabetes in people with high glucose levels who have impaired glucose tolerance and/or impaired fasting glucose. The effect of this drug on both glucose levels and beta-cell mass was studied in a rat model of diabetes, characterized by reduced beta-cell mass at birth with normoglycaemia, and progression to dysglycaemia with age. METHODS: Female Wistar rats were given either saline (vehicle) or nicotine during pregnancy and lactation. Offspring of saline-exposed dams were given vehicle and offspring of nicotine-exposed dams were randomized to receive either vehicle or rosiglitazone starting at weaning. Beta-cell mass, proliferation and apoptosis were determined at birth and at 4 and 26 weeks of age. Glucose homeostasis was examined following sequential oral glucose tolerance tests (OGTT). RESULTS: Rosiglitazone treatment prevented the development of dysglycaemia in nicotine-exposed animals. The ability of rosiglitazone to preserve normoglycaemia appeared to be because of its ability to increase beta-cell mass through a combination of enhanced beta-cell proliferation and decreased beta-cell apoptosis. CONCLUSIONS: These results suggest that if rosiglitazone administration is started prior to the onset of glucometabolic abnormalities, it prevents the onset of dysglycaemia by partially restoring beta-cell mass in animals with reduced beta-cell mass at birth.

Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial.

BACKGROUND: Rosiglitazone is a thiazolidinedione that reduces insulin resistance and might preserve insulin secretion. The aim of this study was to assess prospectively the drug's ability to prevent type 2 diabetes in individuals at high risk of developing the condition. METHODS: 5269 adults aged 30 years or more with impaired fasting glucose or impaired glucose tolerance, or both, and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive rosiglitazone (8 mg daily; n=2365) or placebo (2634) and followed for a median of 3 years. The primary outcome was a composite of incident diabetes or death. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00095654. FINDINGS: At the end of study, 59 individuals had dropped out from the rosiglitazone group and 46 from the placebo group. 306 (11.6%) individuals given rosiglitazone and 686 (26.0%) given placebo developed the composite primary outcome (hazard ratio 0.40, 95% CI 0.35-0.46; p<0.0001); 1330 (50.5%) individuals in the rosiglitazone group and 798 (30.3%) in the placebo group became normoglycaemic (1.71, 1.57-1.87; p<0.0001). Cardiovascular event rates were much the same in both groups, although 14 (0.5%) participants in the rosiglitazone group and two (0.1%) in the placebo group developed heart failure (p=0.01). INTERPRETATION: Rosiglitazone at 8 mg daily for 3 years substantially reduces incident type 2 diabetes and increases the likelihood of regression to normoglycaemia in adults with impaired fasting glucose or impaired glucose tolerance, or both.

Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study.

OBJECTIVE: Despite increasing recognition of schizophrenia as a risk factor for diabetes, the prevalence and correlates of dysglycemia in people with schizophrenia have not been adequately studied. Discerning the modifiable risk factors is crucial for developing diabetes prevention strategies in schizophrenia. METHODS: Socio-demographic, clinical and recent laboratory data were compiled from the case records and supplemental sources of 1123 people treated for schizophrenia who were living across five different communities in the region. RESULTS: Screening rates for fasting plasma glucose (FPG) varied between 63-100% across the five communities, while other metabolic indices were monitored less frequently. 39 subjects (3.5%) in the sample had an existing diagnosis of type 2 diabetes. Among the others, 845 (78%) had FPG measured in the preceding 6 months, with the following results: FPG < or = 5.6 mmol/l in 474 (56%), 5.6-6.9 mmol/l in 268 (31%), and > or = 7 mmol/l in 103 (12.2%) subjects. Dysglycemia (FPG > or = 5.6 mmol/l) was significantly associated with older age (odds ratio [OR] 1.031), longer duration of schizophrenia (OR 1.062), self reported family history of diabetes (OR 8.87), body mass index (OR 1.081), excess weight (OR 1.014) and independent living status (OR 1.779), while European ethnicity (OR 0.706) and regular physical activity (OR 0.958) lowered the risk. No statistically significant correlations were noted with gender, level of education or functioning, or the type of antipsychotic drug prescribed. CONCLUSIONS: There was a two-fold increase in the prevalence of dysglycemia, while there was a substantial under-recognition of and intervention for, diabetes and pre-diabetes in this sample of people treated for schizophrenia.

Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry.

BACKGROUND: Although unstable coronary artery disease is the most common reason for admission to a coronary care unit, the long-term prognosis of patients with this diagnosis is unknown. This is particularly true for patients with diabetes mellitus, who are known to have a high morbidity and mortality after an acute myocardial infarction. METHODS AND RESULTS: Prospectively collected data from 6 different countries in the Organization to Assess Strategies for Ischemic Syndromes (OASIS) registry were analyzed to determine the 2-year prognosis of diabetic and nondiabetic patients who were hospitalized with unstable angina or non-Q-wave myocardial infarction. Overall, 1718 of 8013 registry patients (21%) had diabetes. Diabetic patients had a higher rate of coronary bypass surgery than nondiabetic patients (23% versus 20%, P:<0.001) but had similar rates of catheterization and angioplasty. Diabetes independently predicted mortality (relative risk [RR], 1.57; 95% CI, 1.38 to 1.81; P:<0.001), as well as cardiovascular death, new myocardial infarction, stroke, and new congestive heart failure. Moreover, compared with their nondiabetic counterparts, women had a significantly higher risk than men (RR, 1.98; 95% CI, 1.60 to 2.44; and RR, 1.28; 95% CI, 1.06 to 1.56, respectively). Interestingly, diabetic patients without prior cardiovascular disease had the same event rates for all outcomes as nondiabetic patients with previous vascular disease. CONCLUSIONS: Hospitalization for unstable angina or non-Q-wave myocardial infarction predicts a high 2-year morbidity and mortality; this is especially evident for patients with diabetes. Diabetic patients with no previous cardiovascular disease have the same long-term morbidity and mortality as nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.

Relationship of glucose and insulin levels to the risk of myocardial infarction: a case-control study.

OBJECTIVE: To assess the relationship between dysglycemia and myocardial infarction in nondiabetic individuals. BACKGROUND: Nondiabetic hyperglycemia may be an important cardiac risk factor. The relationship between myocardial infarction and glucose, insulin, abdominal obesity, lipids and hypertension was therefore studied in South Asians-a group at high risk for coronary heart disease and diabetes. METHODS: Demographics, waist/hip ratio, fasting blood glucose (FBG), insulin, lipids and glucose tolerance were measured in 300 consecutive patients with a first myocardial infarction and 300 matched controls. RESULTS: Cases were more likely to have diabetes (OR 5.49; 95% CI 3.34, 9.01), impaired glucose tolerance (OR 4.08; 95% CI 2.31, 7.20) or impaired fasting glucose (OR 3.22; 95% CI 1.51, 6.85) than controls. Cases were 3.4 (95% CI 1.9, 5.8) and 6.0 (95% CI 3.3, 10.9) times more likely to have an FBG in the third and fourth quartile (5.2-6.3 and >6.3 mmol/1); after removing subjects with diabetes, impaired glucose tolerance and impaired fasting glucose, cases were 2.7 times (95% CI 1.5-4.8) more likely to have an FBG >5.2 mmol/l. A fasting glucose of 4.9 mmol/l best distinguished cases from controls (OR 3.42; 95% CI 2.42, 4.83). Glucose, abdominal obesity, lipids, hypertension and smoking were independent multivariate risk factors for myocardial infarction. In subjects without glucose intolerance, a 1.2 mmol/l (21 mg/dl) increase in postprandial glucose was independently associated with an increase in the odds of a myocardial infarction of 1.58 (95% CI 1.18, 2.12). CONCLUSIONS: A moderately elevated glucose level is a continuous risk factor for MI in nondiabetic South Asians with either normal or impaired glucose tolerance.

Serum potassium, cardiovascular risk, and effects of an ACE inhibitor: results of the HOPE study.

BACKGROUND: Both hyper- and hypokalemia increase cardiovascular risk. Modest hyperkalemia is common with angiotensin-converting enzyme inhibition. We studied post-hoc the association of an initial, on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9297 individuals at high cardiovascular risk, randomized to an ACE inhibitor or to placebo. METHODS: Post-hoc analysis of cardiovascular outcomes, as related to serum potassium levels, in the HOPE (Heart Outcomes and Prevention Evaluation) study which compared ramipril to placebo, and included 692 patients with a serum potassium level >5.0 mM and 137 with a serum potassium level <3.5 mM, defined as hyper- and hypokalemia, respectively. Serum potassium was measured 1 month after start of randomized treatment. RESULTS: With hyperkalemia, the primary event rate was unchanged compared to normokalemia (15.5 vs 15.7%, p > 0.4, respectively), with hypokalemia, the primary event rate was higher (22.6% vs 15.5%, respectively, p = 0.023). The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 (1.00-2.06) on multivariate analysis. The combined primary outcome (myocardial infarction, cardiovascular death, stroke) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia. Randomized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo, respectively. The benefit of ramipril on cardiovascular outcomes was independent of serum potassium, but ramipril reduced hypokalemia in the entire cohort (1.15 vs 1.86% with placebo, p = 0.005), particularly in those participants on diuretics (3.8% vs 6.5%, p = 0.07). CONCLUSIONS: In patients at high cardiovascular risk, modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not. Ramipril reduces hypokalemia and decreases risk.

How common is postpartum thyroiditis? A methodologic overview of the literature.

The incidence of postpartum thyroiditis (PPT) in the general population has been reported to range from 1.9% to 16.7%, depending on the study. To determine whether bias may have played a role in the generation of these widely varying estimates, a set of methodologic criteria were applied to the published original research dealing with the epidemiology of PPT. The articles that passed these methodologic filters reported a narrow range of incidences of PPT, varying between 3.7% and 5.9%. Reanalysis of these articles confirmed that thyrotoxicosis occurred more frequently in the first 3 months post partum than did hypothyroidism, and that a positive antimicrosomal antibody titer was strongly associated with postpartum thyroid dysfunction (odds ratio, 86.6; 95% confidence interval, 45.9 to 163.2). This article suggests that PPT is a common condition that occurs in the postpartum period. The best estimate of the incidence of PPT in an unselected cohort of postpartum women is 4.9%.

The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature.

OBJECTIVES: To critically analyze the literature linking microalbuminuria with total and cardiovascular mortality and cardiovascular morbidity in non-insulin-dependent diabetes mellitus (NIDDM) and to quantify the risk. METHODS: A combination of retrieval techniques (MEDLINE, SCISEARCH, and handsearching published bibliographies) was used to find all relevant articles based on title and abstract and "Methods" sections. Unpublished data on albumin excretion rate were sought from large NIDDM cohort studies. RESULTS: A total of 264 citations were retrieved, of which 11 cohort studies were selected for inclusion in the overview, representing a total of 2138 patients followed up for a mean of 6.4 years. Patient age was similar across cohorts. Duration of NIDDM ranged from newly diagnosed to 13 years. The prevalence of microalbuminuria ranged from 20% to 36% in the 8 cohorts that excluded patients with clinical proteinuria. All studies reported either a trend or a significant association between microalbuminuria and total mortality or cardiovascular morbidity or mortality; the overall odds ratio for death was 2.4 (95% confidence interval, 1.8-3.1) and for cardiovascular morbidity or mortality, 2.0 (95% confidence interval, 1.4-2.7). We found no evidence of reporting bias. CONCLUSION: Microalbuminuria is a strong predictor of total and cardiovascular mortality and cardiovascular morbidity in patients with NIDDM.