Change in DASH diet score and cardiovascular risk factors in youth with type 1 and type 2 diabetes mellitus: The SEARCH for Diabetes in Youth Study

Youth with diabetes are at an increased risk of cardiovascular disease (CVD). Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet has been shown to improve CVD risk. In this study, we evaluated whether changes in diet quality as characterized by DASH are associated with changes in CVD risk factors in youth with diabetes over time. Longitudinal mixed models were applied to data from 797 participants in the SEARCH for Diabetes in Youth Study representing three time points: baseline, 12- and 60-month follow-up. Data were restricted to youth whose diabetes was first diagnosed in 2002–2005. DASH-related adherence was poor and changed very little over time. However, an increase in DASH diet score was significantly associated with a decrease in HbA_1c levels in youth with type 1 diabetes (β=−0.20, P-value=0.0063) and a decrease in systolic blood pressure among youth with type 2 diabetes (β=−2.02, P-value=0.0406). Improvements in dietary quality may be beneficial in youth with type 1 or type 2 diabetes. However, further work in larger groups of youth with type 1 and 2 diabetes is desirable.     

2型糖尿病患者校正QT间期延长与多种心血管危险因素的相关性

目的分析QTc延长与多种心血管危险因素的关系。方法除外影响QTc因素的患者后,收集完成糖尿病并发症筛查和12导联心电图检查的数据。根据QTc正常与否（QTc〈0．44S为正常,QTc≥0．44s为延长）,将患者分为正常组和延长组。比较和分析两组患者的多种心血管危险因素。结果人选2型糖尿病患者3426例,其中37％的患者合并有QTc延长。与正常组相比,延长组患者年龄大、糖尿病病程长、女性比例高、腰围和腰臀比大、血压高、心率快,糖化血红蛋白（HbAlc）、餐后2小时血糖、空腹胰岛素、血胆固醇和甘油三酯以及尿白蛋白／肌酐比值高。Logistic回归分析显示,年龄、性别、体质量指数、腰围、腰臀比、心率和血肌酐与QTc延长明显相关。结论略多于1／3的2型糖尿病患者合并QTc延长,并有更多更严重的多种心血管疾病危险因素。     

Association of endothelial dysfunction with cardiovascular risk factors and new‐onset diabetes mellitus in patients with hypertension

Asymmetric dimethylarginine (ADMA), which is the main endogenous inhibitor of nitric oxide synthase, plays a critical role in the process of endothelial dysfunction. The authors evaluated the association between high plasma ADMA levels in patients with hypertension and the presence of cardiovascular risk factors and the development of type 2 diabetes mellitus (DM) and cardiovascular outcomes, including death. The authors evaluated 191 patients with hypertension who were stratified into two groups according to the median value of basal ADMA: those with high levels of plasma ADMA (>0.55 μmol/L) and low levels of plasma ADMA (≤0.55 μmol/L) who were prospectively evaluated over 5.8 years. High ADMA levels were seen in patients with higher weight, body mass index, waist circumference, triglycerides, uric acid, and high‐sensitivity C‐reactive protein, and lower levels of high‐density lipoprotein cholesterol and in patients with type 2 DM. There was an association between high plasma ADMA levels and the occurrence of cardiovascular death. In a subgroup of patients with hypertension free from metabolic syndrome and DM at baseline, there was an association between high ADMA levels and the development of type 2 DM. This study confirms the association of high plasma ADMA levels and the presence of cardiovascular risk factors in patients with hypertension and suggests a positive predictive value of high plasma ADMA levels for cardiovascular death in patients with hypertension and also for the development of type 2 DM in a subgroup of patients with hypertension free from metabolic abnormalities.     

Clustering of cardiovascular risk factors in type 2 diabetes mellitus: prognostic significance and tracking

Summary
Aim   Little attention has been paid to the prognostic significance and tracking effect of risk factor clusters characteristic of type 2 diabetes mellitus. We studied the clustering of eight cardiovascular risk factors (smoking, high body mass index, elevated systolic blood pressure, high serum, low density lipoprotein (LDL) cholesterol, high serum LDL triglycerides, low serum, high density lipoprotein (HDL) cholesterol, high fasting blood glucose and high plasma insulin concentration) and their effect on the prognosis and the tracking effect.
Methods   This study is a population-based prospective follow-up of newly diagnosed type 2 diabetic subjects (n = 133, aged 45–64 years) in Eastern Finland. The following end points were used: all-cause mortality, cardiovascular mortality, and incidences of first myocardial infarction and first stroke. Furthermore, we studied the 'tracking effect' of the risk factor clusters during the 10-year follow-up period.
Results   When the clustering of risk factors typical of type 2 diabetes mellitus was taken into account, all-cause mortality increased from 28.6% to 50.0% (p < 0.05) and cardiovascular disease mortality increased from 14.3% to 50.0% (p < 0.01) depending on the number of risk factors present. The incidence of first myocardial infarction increased from 0% to 40.0% (p < 0.05) as the number of risk factors increased from 0 to 5. In survivors, the proportion of individuals with no risk factors decreased and the proportion on individuals with three to four risk factors increased during the 10-year follow-up period despite the high mortality among the group with many risk factors.
Conclusions   The risk factor clusters among type 2 diabetic subjects are of great predictive value and when not aggressively treated, show a relentless increase despite selective mortality.     

Levels of cardiovascular risk factors in type 2 diabetes mellitus are dependent on the stage of proteinuria.

Levels of cardiovascular risk factors were determined in 75 patients with Type 2 diabetes mellitus. The patients were divided into three groups according to their urinary protein excretion (UPE): (a) normal proteinuria (less than or equal to 70 mg d-1); (b) microproteinuria (70-500 mg d-1); and (c) macroproteinuria (greater than 500 mg d-1). A significant stepwise increase in mean systolic blood pressure, LDL-cholesterol and fibrinogen levels was observed from the first to the third investigated group of patients. Mean apoprotein B levels were significantly increased in the group with macroproteinuria compared to the other two groups. Significant linear correlations were found between UPE and LDL-cholesterol, total cholesterol, apoprotein B, creatinine, systolic blood pressure and diabetes duration. In summary, it is concluded that the levels of some cardiovascular risk factors increase with the stage of proteinuria in Type 2 diabetes mellitus.     

Comparative accuracy of cardiovascular risk prediction methods in patients with diabetes mellitus

SUMMARY
Objective   To compare the accuracy of cardiovascular risk prediction methods based on equations derived from the Framingham Heart Study in a cohort of patients with diabetes mellitus.
Research design and methods   Risk factor data was collected prospectively from 906 patients with diabetes mellitus. Absolute cardiovascular risks were calculated using the Framingham equation, and estimated with the currently available Framingham-based risk tables and charts. The sensitivity, specificity, positive and negative predictive values of the tables and charts to assess cardiovascular risk were assessed using calculation of risk from the full Framingham equation as the reference method.
Results   In all, 146 subjects (16.1%) had calculated 10-year coronary heart disease (CHD) risks ≥ 30%, and 585 (64.6%) had risks ≥ 15%. For identification of those at 10-year CHD risk ≥ 30%, the original Sheffield tables had a sensitivity of 43% (95% confidence intervals (CI) 19.9–61.7%) and specificity of 94% (CI 90.8–96.7%). Modifications of the Sheffield tables improve sensitivity (95% CI 93.9–97%) but reduce specificity (90% CI 85.6–95.7%). The Joint British Guidelines' charts have a moderate sensitivity (69.5% CI 51.8–81.9%) and high specificity (99.7% CI 98.9–100%). For identification of individuals at a 10-year CHD risk ≥ 27%, the Framingham categorical tables had a sensitivity of 95% (CI 91.6–97.8%), but a specificity of only 83% (95% CI 79.1–85.5%).
Conclusions   The Joint British charts appear to have the best performance in a cohort of patients with diabetes mellitus, however, calculation of CHD/CVD (cardiovascular disease) risks with personal or laboratory computers using the full Framingham equation remains the most accurate way to assess cardiovascular risk in a primary prevention setting.     

Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents

Aims:  To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET.
Methods:  The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid-lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and remnant lipoprotein-cholesterol (RLP-C) as well as for determination of LDL particle diameter.
Results:  The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL-C, HDL-C or RLP-C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different.
Conclusions:  The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.     

2型糖尿病患者受教育水平与心血管危险因素的控制：9 921例临床分析

目的分析2型糖尿病患者的受教育水平与心血管危险因素控制的关系。方法收集糖尿病并发症筛查且心血管危险因素等指标资料齐全的2型糖尿病患者的临床资料。按患者受教育程度由低到高分为四组,比较和分析四组患者心血管危险因素控制情况。结果共入选2型糖尿病患者9921例,其中合并两种以上心血管危险因素的患者占57．3％。随着文化水平的升高,女性构成比增加,血压、心率、空腹血糖、餐后血糖、HbAlc、胰岛素抵抗指数、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、尿白蛋白／肌酐比值逐渐降低,血尿酸逐渐升高。总胆固醇、高密度脂蛋白胆固醇、血压、空腹血糖、腰围、HbAlc治疗控制达标率逐渐升高,代谢综合征患病率下降。结论受教育水平低的2型糖尿病患者心血管危险因素的控制率低。有更高的多种心血管危险因素集簇。     

A low carbohydrate Mediterranean diet improves cardiovascular risk factors and diabetes control among overweight patients with type 2 diabetes mellitus: a 1‐year prospective randomized intervention study

Background: The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets are frequently limited by short follow‐up times and high dropout rates. Aim: The effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on health parameters during a 12‐month period. Methods: In this 12‐month trial, 259 overweight diabetic patients (mean age 55 years, mean body mass index 31.4 kg/m²) were randomly assigned to one of the three diets. The primary end‐points were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels. Results: 194 patients out of 259 (74.9%) completed follow‐up. After 12 months, the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet (?2.0 and ?1.6%, respectively, p < 0.022). HDL cholesterol increased (0.1 mmol/l ± 0.02) only on the LCM (p < 0.002). The reduction in serum TG was greater in the LCM (?1.3 mmol/l) and TM (?1.5 mmol/l) than in the ADA (?0.7 mmol/l), p = 0.001. Conclusions: An intensive 12‐month dietary intervention in a community‐based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups. Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control.     

Tumour necrosis factor-alpha plasma levels in elderly patients with Type 2 diabetes mellitus-observations over 2 years.

AIMS: The cytokine tumour necrosis factor-alpha (TNF-alpha) is involved in the development of obesity-linked insulin resistance. TNF-alpha plasma levels rise with increasing age and might thus also be related to metabolic control in Type 2 diabetes mellitus. We have studied the relationship of TNF-alpha plasma levels to glycaemic control in elderly patients with Type 2 diabetes over 2 years. METHODS: Clinical and laboratory data of 53 patients (26 women, 27 men) with Type 2 diabetes (mean age 71.6 +/- 5.6 years) were regularly evaluated over 2 years, and the relationship to anti-diabetic treatment regimens analysed. TNF-alpha plasma level was measured by a solid-phase enzyme amplified sensitivity immunoassay. RESULTS: TNF-alpha plasma levels increased significantly from 16.2 +/- 9.6 pg/ml at baseline to 28.0 +/- 13.8 pg/ml after 2 years (P = 0.028). HbA1c values also increased from 6.4 +/- 1.2% to 7.7 +/- 1.6% (P = 0.046). Mean body mass index of the patients remained almost constant, while a moderate increase in the percentage of body fat (34.5 +/- 7.0% to 35.3 +/- 6.9%; P= 0.061) and in waist-hip ratio was observed (0.86 +/- 0.04 to 0.88 +/- 0.04; P= 0.052). After adjustment for covariates multivariate analysis demonstrated that TNF-alpha plasma levels are positively related to the HbA1c values of the whole study population at the baseline control and after 2 years. TNF-alpha also revealed a positive correlation to the percentage of body fat. CONCLUSIONS: In elderly patients with Type 2 diabetes TNF-alpha plasma levels revealed a continuous increase during an observation period of 2 years. This increase in TNF-alpha plasma levels might add another aspect to the worsening of glycaemic control in the progression of Type 2 diabetes.     

Apolipoprotein B as a long-term predictor of mortality in type 1 diabetes mellitus: a 15-year follow up

OBJECTIVES: To evaluate the association of apolipoprotein B (apo B) with mortality due to all causes, to cardiac disease and to ischaemic heart disease (IHD) in subjects with type 1 diabetes mellitus. SUBJECTS: 165 subjects with type 1 diabetes included in the Swiss Cohort of the WHO Multinational Study of Vascular Disease in Diabetes were followed for 14.7+/-0.45 years. METHODS: Causes of death were obtained from death certificates, hospital records and postmortem reports. Using a parametric proportional hazards model the association of apo B with mortality rates was assessed by time-to-event analysis, including the absolute cumulative mortality risk over time for various apo B levels at baseline. RESULTS: Apo B was positively associated with all-cause mortality [hazard ratio (HR) 2.65 per g L-1 increase of apo B, 95% CI: 1.11-6.36, P=0.029], cardiac mortality (HR 11.64, 1.03-131.11, P=0.047) and IHD mortality (HR 9.36, 1.26-69.66, P=0.029). An apo B>or=0.96 g L-1 translated into a duplication of overall mortality hazard (HR 1.93, 1.00-3.72, P=0.050), and a sevenfold increase of mortality because of cardiac disease or IHD (HR 7.44, 1.44-38.42, P=0.017 and HR 7.38, 0.78-69.82, P=0.081). A baseline apo B of 1.5 g L-1 predicted an absolute cumulative risk to die over the next 10 years of 12.1% (5.2-31.7) for male and of 10.4% (4.7-26.1) for female subjects whereas risks were 6.3% (1.8-21.4) and 5.4% (0.8-15.8) for an apo B of 0.8 g L-1. CONCLUSION: Apo B is consistently associated with an increased mortality in type 1 diabetes.     

Effects of liraglutide on cardiovascular risk factors in patients with type 1 diabetes

We investigated the short‐term effect of adding liraglutide 1.8 mg once daily to insulin treatment on cardiovascular risk factors in patients with type 1 diabetes. In total, 100 overweight (BMI ≥25 kg/m²) adult patients (age ≥18 years) with type 1 diabetes and HbA1c ≥ 8% (64 mmol/mol) were randomized to liraglutide 1.8 mg or placebo added to insulin treatment in a 24‐week double‐blinded, placebo‐controlled trial. At baseline and after 24 weeks of treatment, 24‐hour blood pressure and heart rate, pulse pressure, pulse wave velocity and carotid intima‐media thickness were evaluated. Compared with placebo, liraglutide increased 24‐hour heart rate by 4.6 beats per minute (BPM); P = .0015, daytime heart rate by 3.7; P = .0240 and night‐time heart rate by 7.5 BPM; P < .001 after 24 weeks. Diastolic nocturnal blood pressure increased by 4 mm Hg; P = .0362 in the liraglutide group compared with placebo. In conclusion, in patients with long‐standing type 1 diabetes, liraglutide as add‐on to insulin increased heart rate and did not improve other cardiovascular risk factors after 24 weeks of treatment.     

Screening cardiovascular risk factors of diabetes patients in the primary diabetes clinics

To evaluate the atherosclerotic cardiovascular diseases (ASCVD) risk factors in type 2 diabetes patients from the primary diabetes clinics for further comprehensive intervention in China.A cross-sectional study was conducted in 5 primary diabetes chain hospitals in Beijing, Lanzhou, Harbin, Chengdu, and Taiyuan in continuous patients with type 2 diabetes from March 2016 to December 2019. The data collected at the first visit were analyzed, and proportions of patients reached the targets (glycosylated hemoglobin [HbA₁c] < 7%, blood pressure < 130/80 mm Hg, and low-density lipoprotein cholesterol [LDL-C] < 2.6mmol/l) were calculated. The clinical characteristics and the associated factors with achievement in HbA₁c, blood pressure, and LDL-C targets were analyzed.A total of 20,412 participants, including 11,353 men (55.6%), with an average age of (59.4 ± 10.4) years were enrolled. Nearly 95% diabetes had one or more ASCVD risk factors other than hyperglycemia. The control rates of HbA₁c, blood pressure, and LDL-C were 26.5%, 27.8%, and 42.6%, respectively. Only 4.1% patients achieved all 3 targets. Nearly 95% patients had one or more ASCVD risk factors other than hyperglyciemia. Diabetes duration, family history, and overweight/obesity were associated with the number of aggregated ASCVD risk factors. The patients with older age, no overweight/obesity, not smoking, less ASCVD risk factors, and having special diabetes care insurance (Chengdu) were associated with a higher control rates.To deal with poor control status, global management of ASCVD risk factors, weight loss, and smoking cessation must be emphasized in the primary diabetes care settings. Special diabetes care insurance should be advocated.Current ClinicalTrial.gov protocol ID {"type":"clinical-trial","attrs":{"text":"NCT03707379","term_id":"NCT03707379"}}NCT03707379. Date of Registration: October 16, 2018. https://clinicaltrials.gov.     

2型糖尿病尿微量白蛋白与心血管病危险因素的研究

目的探讨2型糖尿病（T2DM）患者尿微量白蛋白与心血管病危险因素（血糖、血脂、血压、尿酸等）的关系。方法选择192例确诊为T2DM住院患者,分为微量白蛋白尿（MAU）组（n=60）和正常微量白蛋白尿（NAU）组（n=132）,检测患者体质指数（BMI）、血脂、血压、尿酸等相关危险因素,并进行对比分析;同时以尿微量白蛋白为因变量,各相关危险因素为自变量进行了多元线性回归分析,以明确影响2型糖尿病患者尿微量白蛋白增加的因素。结果 MAU组糖化血红蛋白水平（HbA1c）、入院时收缩压（SBP）、舒张压（DBP）水平、血肌酐（Cr）、尿酸（UA）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）水平及TC、LDL-C、UA、SBP和DBP的异常率明显高于NAU组,而高密度脂蛋白胆固醇（HDL-C）水平明显低于NAU组（P〈0.05～0.01）,多元线性回归分析发现MAU与BMI、SBP、DBP、TC、TG、LDL-C、HbA1c、UA和Cr呈正相关,而与HDL-C呈负相关（P〈0.05～0.01）。结论血脂、血压等多种危险因素的异常影响T2DM患者尿微量白蛋白水平。     

Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations

Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT-2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG-OUTCOME, CANVAS and DECLARE-TIMI 58) and real-world evidence studies (CVD-REAL, EASEL, CVD-REAL 2 and OBSERVE-4D). A series of clinical recommendations on the use of SGLT-2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.     

THE metabolic syndrome and accurate cardiovascular risk prediction in persons with type 2 diabetes mellitus

BackgroundPersons with type 2 DM have a cardiovascular risk 2–4 times that of the normal population. Co-occurrence of metabolic syndrome (MS) with type 2 DM is associated with an increased risk of development of cardiovascular disease. The aim of this study was to determine the prevalence of the MS in patients with type 2 diabetes mellitus and to compare absolute cardiovascular risk in type 2 DM Patients with MS with those without MS.MethodsAnthropometric measurements and Blood Pressure of 340 eligible patients with type 2 DM recruited into the study were taken. Participants’ FPG, FLP and glycated haemoglobin were also estimated. Cardiovascular risk score was calculated using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Diagnosis of the MS was the International Diabetes Federation Criteria (IDF).ResultsOver 66% participants had MS. The absolute cardiovascular risk score was found to be similar in persons with type 2 DM whether they fulfilled the criteria for diagnosis metabolic syndrome or not.ConclusionThe absolute cardiovascular risk score was similar in type 2 DM patients with or without the metabolic syndrome.     

Sex- and BMI-related differences in risk factors for coronary artery disease in patients with type 2 diabetes mellitus

There are contrasting data about the relationship between obesity and macrovascular complications in type 2 diabetes mellitus, and it is not known if risk factors for coronary artery disease are different in normal weight and overweight or obese patients. All 2113 patients with type 2 diabetes mellitus referring to the Diabetic Clinic of Asti were studied. Patients were divided into tertiles of body mass index, according to their sex (BMI < 26.9; ≥ 26.9 and < 31.4; ≥ 31.4 kg/m² for females and BMI < 25.7; ≥ 25.7 and < 28.8; ≥ 28.8 kg/m² for males). Age, BMI, duration of diabetes, blood pressure, HbA_1c total cholesterol, HDL-cholesterol, LDL-cholesterol, and prevalence of insulin treatment and hypertension were higher in females, whereas exercise, alcohol intake, smoking habits and prevalence of dyslipidemia were higher in males. An increase in BMI was associated with an increase in HbA_1c, number of cigarettes/day, blood pressure, triglycerides, C-peptide, prevalence of hypertension and dyslipidemia, and with a decrease in age, duration of diabetes and HDL-cholesterol values. In spite of an apparently worse cardiovascular risk profile, females showed a 50% lower prevalence of CAD than males and the prevalence of CAD was not significantly different in obese compared to other BMI categories. Multiple logistic regression showed that risk factors for CAD were different in males and females and similar in the lower tertiles of BMI, while different in the highest. In obese females, risk factors for CAD were age, reduced HDL-cholesterol and increased HbA_1c levels; in males they were years of smoking and duration of diabetes. These data suggest that in type 2 diabetes, risk factors for CAD are different in the two sexes and in patients with the highest BMI compared to the normal and overweight subjects; blood glucose control and duration of diabetes seem more important than conventional cardiovascular risk factors in obese patients. Received: 11 May 1998 / Accepted in revised form: 30 July 1999     

Troglitazone reduces plasma levels of tumour necrosis factor-alpha in obese patients with type 2 diabetes

We evaluated the effect of troglitazone (given orally 400 mg/day) on glucose intolerance and on the plasma levels of tumour necrosis factor-alpha (TNF-alpha) in 12 obese patients with type 2 diabetes for 12 weeks. Troglitazone significantly decreased fasting plasma glucose, serum C-peptide, serum insulin and HbA1c levels. Plasma levels of TNF-alpha were significantly reduced by troglitazone administered for 8 and 12 weeks. Troglitazone administration significantly improved insulin resistance, but did not affect pancreatic beta-cell function as evaluated by the homeostasis model assessment (HOMA). In the present study, we reported for the first time that troglitazone administration significantly reduces plasma levels of TNF-alpha in obese patients with type 2 diabetes.     

Insulin receptor substrate-1 gene polymorphism and cardiovascular risk in non-insulin dependent diabetes mellitus and patients undergoing coronary angiography

Clustering of risk factors for cardiovascular disease related to insulin resistance may account for the increased incidence of vascular disease in these conditions and in non-diabetic subjects. To investigate the relationship between a coding polymorphism in the insulin receptor substrate-1 gene and the presence of cardiovascular risk factors, 209 patients with NIDDM and 452 subjects investigated for coronary artery disease (CAD) were studied. In the NIDDM subjects 22 (10.5%) were heterozygous at codon 972 for a polymorphism which codes for a glycine to arginine substitution and 187 (89.5%) were homozygous for the wild type. Patients with the mutation had lower levels of cholesterol compared with wild type (mean, 95% confidence intervals), 5.3 (4.9–5.8) vs 6.0 (5.9–6.2) mmol/l, respectively (P = 0.002), triglyceride 1.7 (1.4–2.1) vs 2.2 (2.0–2.4) mmol/l (P = 0.051), factor VII:C activity 109.5 (85.5–133.5) vs 133.5 (127–140)% (P = 0.057) and PAI-1 antigen, 16.0 (10.5–24.3) vs 22.2 (20.0–24.6) ng/ml (P = 0.054). There were no differences in body mass index, indices of glycaemic control, fasting insulin or the prevalence of hypertension. In patients with CAD, 55 (12.7%) were carriers of the mutation (including three homozygotes) (NIDDM vs CAD, NS). Although similar trends in cholesterol, factor VII, PAI-1 antigen and triglyceride existed between carriers of the mutation and the wild type, none reached statistical significance. The results indicate that the IRS-1 gene is not implicated in the pathogenesis of NIDDM or CAD.