Maternal arterial stiffness in pregnancies affected by Type 1 diabetes mellitus

Aim There is little information about maternal central haemodynamics and arterial stiffness in pregnancies affected by Type 1 diabetes mellitus. The aim of the current study was to investigate whether maternal arterial stiffness is altered in pregnant women with Type 1 diabetes mellitus compared with women with uncomplicated pregnancies. Methods This was a cross‐sectional study involving 37 pregnant women without diabetes and 37 pregnant women with Type 1 diabetes mellitus during the second trimester of pregnancy. Maternal wave reflection (augmentation index) and pulse wave velocity of the carotid‐femoral and carotid‐radial part of the arterial tree were assessed non‐invasively using applanation tonometry. Results Pregnant women with normal pregnancies and Type 1 diabetes mellitus had similar augmentation index (3.7 ± 12.8 vs. 5.1 ± 12.6%, P = 0.6), even after adjusting for possible confounders. Within the group of diabetic women, augmentation index was associated with duration of diabetes (P = 0.003, r² = 0.22) but not with glycated haemoglobin. Pulse wave velocities were similar between the two groups of women (carotid‐femoral: 5.6 ± 0.9 vs. 5.7 ± 1.1 m/s, P = 0.4; carotid‐radial: 7.4 ± 1.2 vs. 7.8 ± 1 m/s, P = 0.1). In the diabetic women there was no significant association between the pulse wave velocities and either duration of diabetes or glycated haemoglobin. Conclusions Pregnancy in women with Type 1 diabetes mellitus is not associated with altered maternal systemic arterial stiffness. However, maternal wave reflections increase with the duration of diabetes.     

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults

Introduction Confirmation of monogenic diabetes caused by glucokinase mutations (GCK‐MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK‐MODY is most prevalent. Methods The study evaluated the utility of lipid parameters in screening for patients with GCK‐MODY. Eighty‐nine children with type 1 diabetes and 68 with GCK‐MODY were screened for triglyceride (TG), total and HDL cholesterol levels. Standardization against a control group of 171 healthy children was applied to eliminate the effect of development. Clinical applicability and cut‐off value were evaluated in all available patients with GCK‐MODY (n = 148), hepatocyte nuclear factor 1‐alpha‐MODY (HNF1A MODY) (n = 37) or type 1 diabetes (n = 221). Results Lower lipid parameter values were observed in GCK‐MODY than in patients with type 1 diabetes. Standard deviation scores were ?0·22 ± 2·24 vs 1·31 ± 2·17 for HDL cholesterol (P < 0·001), ?0·16 ± 2·14 vs 0·60 ± 1·77 for total cholesterol (P = 0·03) and ?0·57 ± 0·97 vs?0·22 ± 0·97 for TG (P = 0·05). Validation analysis confirmed that HDL cholesterol was the best parameter for GCK‐MODY selection [sensitivity 87%, specificity 54%, negative predictive value (NPV) 86%, positive PV 56%]. A threshold HDL concentration of 1·56 mm offered significantly better diagnostic efficiency than total cholesterol (cut‐off value 4·51 mm ; NPV 80%; PPV 38%; P < 0·001). TG did not offer a meaningful cut‐off value. Conclusions HDL cholesterol levels measured in individuals with likely monogenic diabetes may be useful in screening for GCK‐MODY and differentiation from T1DM and HNF1A‐MODY, regardless of treatment or metabolic control.     

Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats

Abstract: The study objective was to investigate the effects of melatonin on obesity and obesity‐associated systolic hypertension and dyslipidemia in young male Zucker diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome. ZDF rats (n = 30) and lean littermates (ZL) (n = 30) were used. At 6 wk of age, both lean and fatty animals were subdivided into three groups (n = 10): naive (N), vehicle‐treated (V), and melatonin‐treated (M) (10 mg/kg/day) for 6 wk. Vehicle and melatonin were added to the drinking water. Melatonin reduced mean weight gain (51 ± 2/100 g BW) versus N‐ZDF group (58 ± 3, P < 0.05) without food intake differences. M‐ZDF rats showed an apparent reduction in systolic hypertension that proved not to be statistically significant, and a significant improvement in dyslipidemia, with a reduction in hypertriglyceridemia from 580 ± 40 to 420.6 ± 40.9 mg/dL (P < 0.01). Melatonin raised high‐density‐lipoprotein (HDL) cholesterol in ZDF (from 81.6 ± 4.9 to 103.1 ± 4.5 mg/dL, P < 0.01) and ZL rats (from 62.8 ± 4.8 to 73.5 ± 4.8 mg/dL, P < 0.05) and significantly reduced low‐density‐lipoprotein (LDL) cholesterol in ZDF rats from 5.20 ± 0.4 to 4.14 ± 0.3 mg/dL (P < 0.05) but had no effect on total cholesterol levels. To our knowledge, this is the first evidence of a positive effect of melatonin on overweight and lipid pattern of obese Zucker diabetic rats, supporting the proposition that melatonin administration may ameliorate overweight and lipid metabolism in humans. Because these benefits occurred in youth, before advanced metabolic and vascular complications, melatonin might help to prevent cardiovascular disease associated with obesity and dyslipidemia.     

Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers,vascular tone,inflammation, oxidative stress and insulin sensitivity

Objective Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid‐rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high‐risk cardiovascular subjects with Type 2 diabetes. Research design and methods Thirty‐two Type 2 diabetes mellitus patients, prescribed diet or oral glucose‐lowering agents, received GSE (600 mg/day) or placebo for 4 weeks in a double‐blinded randomized crossover trial. Markers of endothelial function (measured by photoplethysmography), oxidative stress [total antioxidant status (TAOS), reduced glutathione (GSH)/oxidized glutathione (GSSG)], inflammation [highly sensitive C‐reactive protein (hsCRP), urinary albumin : creatinine ratio), insulin resistance [homeostasis model assessment–insulin resistance (HOMA–IR)] and metabolism (fructosamine, lipid profile) was measured at baseline and after intervention with GSE or placebo. Results Baseline characteristics (16 male and 16 female): age 61.8 ± 6.36 years; body mass index 30.2 ± 5.92 kg/m²; diabetes duration 5.9 ± 2.14 years. Following GSE (but not placebo), significant changes were noted in fructosamine (282 ± 40.9 vs. 273 ± 50.2 mmol/l; P = 0.0004); whole blood GSH (2359 ± 823 vs. 3595 ± 1051 mmol/l; P < 0.01) and hsCRP (3.2 ± 3.65 vs. 2.0 ± 2.2 mg/l; P = 0.0006). Total cholesterol concentration also decreased (4.5 ± 0.96 vs. 4.3 ± 0.99 mmol/l; P = 0.05). No statistically significant changes were shown in endothelial function, HOMA–IR or TAOS. Conclusion GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4‐week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk.     

Improved retention rates with low-cost interventions in hypertension and diabetes management in a rural African environment of nurse-led care: a cluster-randomised trial

Objective To compare the effects of low‐level facility‐based interventions on patient retention rates for cardiovascular (CV) disease in an environment of task shifting and nurse‐led care in rural health districts in Central Cameroon. Methods This study is an open‐label, three‐arm, cluster‐randomised trial in nurse‐led facilities. All three groups implemented a treatment contract. The control group (group 1) had no additional intervention, group 2 received the incentive of 1 month of free treatment every forth month of regularly respected visits, and group 3 received reminder letters in case of a missed follow‐up visit. The primary outcome was patient retention at 1 year. Secondary outcomes were adherence to follow‐up visit schemes and changes in blood pressure (BP) and blood glucose levels. Patients’ monthly spending for drugs and transport was calculated retrospectively. Results A total of 33 centres and 221 patients were included. After 1 year, 109 patients (49.3%) remained in the programme. Retention rates in groups 2 and 3 were 60% and 65%, respectively, against 29% in the control group. The differences between the intervention groups and the control group were significant (P < 0.001), but differences between the two intervention groups were not (P = 0.719). There were no significant differences in BP or fasting plasma glucose trends between retained patients in the study groups. Average monthly cost to patients for antihypertensive medication was € 1.1 ± 0.9 and for diabetics €1.2 ± 1.1. Transport costs to the centres were on average €1.1 ± 1.0 for hypertensive patients and €1.1 ± 1.6 for patients with diabetes. Conclusions Low‐cost interventions suited to an environment of task shifting and nurse‐led care and needing minimal additional resources can significantly improve retention rates in CV disease management in rural Africa. The combination of a treatment contract and reminder letters in case of missed appointments was an effective measure to retain patients in care.     

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland Study design and 1-year interim report on the feasibility of the lifestyle intervention programme

Aims/hypothesis. The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. Methods. A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. Results. During the first year, weight loss in the first 212 study subjects was 4.7 ± 5.5 vs 0.9 ± 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 ± 0.7 vs 6.4 ± 0.8 mmol/l, p < 0.001; and 2-h 7.8 ± 1.8 vs 8.5 ± 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. Conclusion/interpretation. The interim results show the efficacy and feasibility of the lifestyle intervention programme. [Diabetologia (1999) 42: 793–801] Received: 7 December 1998 and in revised form: 23 February 1999     

Improved glycaemic control and treatment satisfaction with a simple wearable 3‐day insulin delivery device among people with Type 2 diabetes

Aim

To evaluate the PAQ^® (CeQur SA, Horw, Switzerland), a wearable 3‐day insulin delivery device that provides set basal rates and bolus insulin on demand, in people with Type 2 diabetes.

Method

Adults with Type 2 diabetes with HbA_1c concentrations ≥53 and ≤97 mmol/mol (7.0 and 11.0%) while treated with ≥2 insulin injections/day were enrolled in two single‐arm studies comprising three periods: a baseline (insulin injections), a transition and a PAQ treatment period (12 weeks). Endpoints included HbA_1c, seven‐point self‐monitored blood glucose, total daily dose of insulin and body weight. Safety was assessed according to examination, hypoglycaemic episodes and adverse device effects.

Results

A total of 28 adults were enrolled (age 63 ± 7 years, 86% men, BMI 32.3 ± 4.3kg/m², Type 2 diabetes duration 17 ± 8 years, HbA_1c 70 ± 12 mmol/mol (8.6 ± 1.1%), total daily insulin dose 58.7 ± 20.7 U), of whom 24 completed the studies. When transitioned to PAQ, 75% of participants continued on the first basal rate selected. After 12 weeks of PAQ wear, significant improvements from baseline were seen [HbA_1c –16 ± 9 mmol/mol (95% CI –20, –12) or –1.5 ± 0.9% (95% CI –1.8, –1.1) P<0.0001], and at all seven self‐monitored blood glucose readings time points (P ≤0.03). Total daily insulin dose increased by 12.1 ± 19.5 U (95% CI 3.9, 20.4; P=0.0058), the number of meal time boluses increased by 0.9 ± 1.5/day (95% CI 0.3, 1.5; P=0.0081) and body weight remained stable. Six participants had mild to moderate catheter site reactions and one mild skin irritation occurred. No participant experienced severe hypoglycaemia.

Conclusions

Adults with Type 2 diabetes were safely transitioned from insulin injections to the PAQ and had significantly improved glycaemic control and treatment satisfaction with insulin therapy. (ClinicalTrials.gov identifiers: NCT02158078 & NCT02419859)     

Biphasic insulin aspart‐30 reduces glycemic variability to a greater degree than insulin detemir: A randomized controlled trial of once‐daily insulin regimens using continuous glucose monitoring

Introduction

We compared the efficacy of insulin detemir and biphasic insulin aspart‐30 given in the morning as an add‐on to oral hypoglycemic agents in type 2 diabetes patients.

Materials and Methods

The present study enrolled 30 patients with poorly controlled type 2 diabetes (8% ≤ glycated hemoglobin < 11%) being treated with oral hypoglycemic agent mono‐ or combination therapy with biguanides, sulfonylureas or thiazolidinediones. The patients were randomly assigned to insulin detemir (group D) or insulin aspart‐30 (group A) given in the morning as add‐on to oral hypoglycemic agents. After adjusting their insulin doses, the patients that underwent continuous glucose monitoring during a 3‐day hospitalization and with day 2 continuous glucose monitoring data were subjected to analysis.

Results

There was no significant difference in patient background, baseline glycated hemoglobin levels and insulin doses during continuous glucose monitoring between the two groups. The percent coefficient of variation of 24‐h glucose levels was significantly lower in group A (20.4 ± 7.6) than in group D (27.1 ± 6.5; P = 0.015). Similarly, mean amplitude of glycemic excursions was significantly smaller in group A (80 ± 32) than in group D (102 ± 14; P = 0.021). Postprandial glucose excursions were significantly smaller after breakfast in group A (65 ± 31 mg/dL) than in group D (106 ± 32 mg/dL; P = 0.002).

Conclusions

As once‐daily insulin injection therapy given before breakfast in type 2 diabetes patients, the biphasic insulin analog might represent a better insulin option in significantly lowering the percent coefficient of variation and mean amplitude of glycemic excursions than the long‐acting insulin preparation.     

The effect of biopsy‐positive silent coeliac disease and treatment with a gluten‐free diet on growth and glycaemic control in children with Type 1 diabetes

Objective To determine the effect of coeliac disease and treatment with a gluten‐free diet on growth and glycaemic control in asymptomatic children with Type 1 diabetes. Methods Data were compared in children with coeliac disease diagnosed by annual antibody screening and jejunal biopsy and treated with a gluten‐free diet (n = 49) against individuals who were antibody negative (n = 49) matched for age, sex and duration of diabetes. Results No differences in growth were observed. In the years prior to diagnosis of coeliac disease, mean glycated haemoglobin (HbA_1c) was lower in cases compared with control subjects [8.3 ± 1.1% vs. 8.7 ± 0.9%, P = 0.02 (mean ± sd )]. In cases, HbA_1c deteriorated 12 months from the start of a gluten‐free diet to levels similar to control subjects (8.9 ± 1.5% vs. 8.8 ± 1.5%, P‐value for analysis of variance = 0.9). In regression analysis, the diagnosis of coeliac disease and start of a gluten‐free diet was associated with a rise in HbA_1c in the first year of treatment [odds ratio 1.56 (95% confidence intervals 1.16–2.10), P = 0.003] after adjusting for insulin dose and regimen and other variables. Conclusions In children with Type 1 diabetes, lower HbA_1c prior to diagnosis of silent coeliac disease rises following treatment with a gluten‐free diet to levels similar to those without coeliac disease. Although unproven, these observations may relate to abnormalities at the small bowel mucosa before the appearance of circulating coeliac antibodies.     

Determinants of carotid artery wall thickening in young patients with Type 1 diabetes mellitus

To investigate associations between early atherosclerosis and possible risk factors for it in young patients with established Type 1 diabetes mellitus (DM), we measured the combined intima-media thickness (IMT) of the common carotid arteries with high resolution ultrasound in 310 young patients (age ≤ 40 years, mean 27.9 ± 6.5) with a diabetes duration ≥ 2 years, and in two control groups of similar age (control 1:40 healthy subjects, control 2: 40 Type 1 DM recently diagnosed patients). Albumin excretion rate and lipids (total cholesterol and triglycerides) were measured and retinopathy and hypertension (systolic blood pressure > 140 or diastolic blood pressure > 90 mmHg) sought in the patients. Mean maximum IMT was 0.52 ± 0.06 mm in control group 1 and 0.50 ± 0.05 mm in control group 2 with a mean difference of 0.02 mm (95% CI: −0.01, 0.04). The more established Type 1 DM patients had a significantly greater IMT (0.57 ± 0.13 mm, p < 0.001) than both control groups. In a subgroup analysis, patients with microvascular diabetic complications (n = 99) had a significantly greater IMT (0.63 ± 0.17 vs 0.55 ± 0.10 mm, p < 0.001) than those without (n = 211). In a multiple linear regression analysis with a significance level of ≤ 0.10, the carotid artery IMT of our established diabetic patients was related to age, male gender, triglycerides and nephropathy, suggesting the latter as the main diabetes-specific risk for intima-media thickening in young Type 1 DM patients. © 1998 John Wiley & Sons, Ltd.     

Causes of weight gain during insulin therapy with and without metformin in patients with Type II diabetes mellitus

Aims/hypothesis. To determine causes of weight gain during insulin therapy with and without metformin in Type II (non-insulin-dependent) diabetes mellitus. Methods. Twenty-six patients with Type II diabetes (body mass index 28 ± 1 kg/m²) were treated with insulin alone (n = 13) or insulin and with metformin (n = 13). Components of energy balance (basal metabolic rate, energy intake, glucosuria) were measured at 0 and 12 months. Results. Glycaemic control improved similarly in patients using (HbA_{1 c} 10.5 ± 0.3 vs 7.6 ± 0.2 %, p < 0.001) and not using (10.2 ± 0.3 vs 7.8 ± 0.3 %, p < 0.001) metformin. The metformin group required 47 % less insulin than the group not using metformin (p < 0.001). Body weight increased by 3.8 ± 0.8 and 7.5 ± 1.6 kg (p < 0.05), respectively. Basal metabolic rate and glucosuria were similar at 0 and 12 months in both groups but the metformin group decreased energy intake by 1.12 ± 0.46 MJ/day, whereas it remained unchanged in the other group (0.15 ± 0.42 MJ/day). Changes in body weight and glycaemia were statistically significant independent determinants of basal metabolic rate. Their change in opposite directions explained why basal metabolic rate remained unchanged. Conclusion/interpretation. Improved glycaemia promotes weight gain by decreasing both basal metabolic rate and glucosuria. Use of metformin decreases weight gain by reducing energy intake and is therefore a useful adjunct to insulin therapy in patients with Type II diabetes. [Diabetologia (1999) 42: 406–412] Received: 3 September 1998 and in final revised form: 4 December 1998     

Glycaemic and nonglycaemic effects of pioglitazone in triple oral therapy of patients with type 2 diabetes

Objectives. To examine pioglitazone as add‐on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and β‐cell function (proinsulin/insulin) and fluid retention. Design and setting. Prospective open‐label study of 54 patients with type 2 diabetes and HbA_1c≥6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30–45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one‐third of patients were followed for 3 months without pioglitazone. Results. HbA_1c decreased (7.8 ± 0.9–6.3 ± 0.9%, P < 0.001) with 61% of patients achieving levels <6.5%. However, in the group followed for another 3 months HbA_1c increased (6.1 ± 0.73–7.1 ± 0.9, n = 18, P < 0.001) after pioglitazone withdrawal. Adiponectin increased (6.1 ± 2.8–13.2 ±5.8 μg mL^?1, P < 0.001) and the proinsulin to insulin ratio decreased (0.89 ± 0.66–0.66 ± 0.53, P < 0.001). Nt‐proBNP increased from 487.3 ± 252.2 to 657.8 ± 392.1 pmol L^?1 (P < 0.001). Conclusions. Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving β‐cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt‐proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.     

Growth Hormone Levels in Patients with Type 1 Diabetes are Age Related

Possible effects of age on the growth hormone (GH) levels in Type 1 diabetes were examined. The study was performed in 71 patients with Type 1 diabetes (40 C-peptide negative (CpN), without residual beta cell activity; 31 C-peptide positive (CpP), with preserved beta cell activity) and 11 healthy subjects. The patients and controls were divided into three age groups (A = 21–30; B = 31–40; C = 41–50 years). Blood glucose and growth hormone (GH) were measured at hourly intervals during 24 h in all subjects in hospital conditions. GH levels decreased significantly with age in patients with Type 1 diabetes (mean 24-h GH group A: 7.3 ± 1.0, group B:5.3 ± 0.6, group C:3.7 ± 0.4 mU 1^?1; A vs C: p = 0.0007; B vs C: p = 0.03). In all age groups GH levels were significantly higher in CpN than either in CpP diabetic patients or controls (group A CpN: 8.3 ± 1.2, CpP: 4.7 ± 1.0, controls: 2.2 ± 0.3 mU 1^?1; p < 0.001; group B CpN: 7.3 ± 0.8, CpP: 3.2 ± 0.5, controls: 1.6 ± 1.0 mU 1^?1; p < 0.0002; group C CpN: 5.2 ± 0.5, CpP: 2.5 ± 0.4, controls: 1.4 ± 0.4 mU 1^?1; p < 0.001). Mean GH levels were significantly higher in C-peptide positive patients than in controls in all age groups (p < 0.001). GH levels decreased with age in patients with diabetes and controls, but the decrease was significant only in patients with diabetes (A vs C CpN: p = 0.018, CpP: p = 0.026). We conclude that age is a factor in addition to residual beta cell activity, which influences the magnitude of GH hypersecretion in Type 1 diabetes.     

原发性高血压并发初发糖尿病的相关因素

目的 分析原发性高血压并发初发糖尿病的相关因素。 方法 搜集2013年6月~2016年6月陕西省人民医院心内科收住入院诊断高血压病并发从未使用药物治疗的新诊断2型糖尿病患者468例作为并发糖尿病组。与同期入院诊断单纯原发性高血压患者468例作为对照组（非糖尿病组）比较分析。 结果 并发糖尿病组与非糖尿病组比较,体质量指数〔（28.8±3.9） kg/m2 vs.（25.1±3.2） kg/m2,P<0.05〕、HbA1c〔（9.4±1.6）% vs.（6.0±0.4）%,P<0.05〕、总胆固醇（TC）〔（4.8±1.4） mmol/L vs.（3.2±0.8） mmol/L,P<0.05〕、三酰甘油（TG）〔（2.2±1.3） mmol/L vs.（1.6±0.8） mmol/L,P<0.05〕均具有统计学意义。多因素Logistic分析回归分析显示TC、TG偏高为原发性高血压并发初发糖尿病危险因素,OR值分别为2.349（95%Cl:2.10-3.308）、1.903（95%Cl:1.508-2.267）;以HbA1c为因变量,体质量指数、TC、TG、低密度脂蛋白胆固醇为自变量行重线性回归分析,HbA1c与TC成正相关,回归方程为:HbA1c=1.309＋1.626×TC,P<0.01。 结论 TG、TC水平升高是高血压病并发初发糖尿病患者的危险因素,并且HbA1c与TC呈正相关。     

A pilot urban church-based programme to reduce risk factors for diabetes among Western Samoans in New Zealand

We have assessed the impact of a 2-year pilot church-base diabetes risk reduction programme on major lifestyle predictors of future Type 2 diabetes mellitus: exercise and weight control in a prospective non-randomized controlled study of a modular lifestyle and diabetes awareness intervention programme using a community development model. The study involved two complete church congregations from an ethnic group at high risk of diabetes (Western Samoans) (intervention church n = 78; control church n = 144). Weight remained stable (0 ± 4.8 kg) in the intervention church but increased by 3.1 ± 9.8 kg in the control church (p = 0.05). In the intervention church, there was an associated reduction in waist circumference (−4 ± 10 cm vs +2 ± 7 cm in control, p < 0.001), an increase in diabetes knowledge (46 ± 26 % vs 4 ± 17 % in control, p < 0.001) and an increase in the proportion exercising regularly (+22 % vs −8 % in control, p < 0.05). Consumption of key fatty foods was also reduced in the intervention church. We conclude that diabetes risk reduction programmes based upon lifestyle change, diabetes awareness, and empowerment of high risk communities can significantly reduce risk factors for future Type 2 diabetes. © 1998 John Wiley & Sons, Ltd.     

Nateglinide combination therapy with basal insulin and metformin in patients with Type 2 diabetes

Aims To compare the effect of adding nateglinide or placebo on postprandial glucose excursions (PPGEs), glycated haemoglobin (HbA_1c), diurnal glucose profiles and hypoglycaemia in patients with Type 2 diabetes treated with the combination of basal insulin and metformin. Research design and methods This was an investigator‐initiated, double‐blind, randomized, parallel‐group, study in five centres. Patients with Type 2 diabetes (n = 88, age 56.0 ± 0.9 years, duration of diabetes 9.4 ± 0.5 years, HbA_1c 7.8 ± 0.1%, body mass index 32.4 ± 0.5 kg/m²) treated with basal insulin and metformin entered a 24‐week period, during which basal insulin was titrated to optimize glucose control. Thereafter, the patients were randomized to receive either nateglinide (120 mg three times daily) or placebo before their main meals for 24 weeks. Results During the optimization period, HbA_1c decreased by ?0.3 ± 0.1 and ?0.4 ± 0.2% (NS) and insulin doses increased by 10.0 IU (2.0–32.0) [0.09 IU/kg (0.02–0.34)] and 10.0 IU (0.0–19.0) [0.11 IU/kg (0.0–0.25)] (NS) in the nateglinide and placebo groups. Mean postprandial glucose during weeks 20–24 averaged 9.0 ± 0.3 and 10.0 ± 0.3 mmol/l in the nateglinide and placebo groups (P = 0.025) and mean PPGE averaged 2.4 ± 0.2 and 3.1 ± 0.2 mmol/l, respectively (P = 0.019). At 24 weeks as compared with 0 weeks, mean HbA_1c had decreased by 0.41 ± 0.12% in the nateglinide group and by 0.04 ± 0.12% in the placebo group (P = 0.023). The frequency of confirmed, symptomatic hypoglycaemia was 7.7 episodes/patient‐year vs. 4.7 episodes/patient‐year in the nateglinide and placebo groups (P = 0.031). Conclusions Addition of a short‐acting insulin secretagogue at main meals improves postprandial hyperglycaemia during combination therapy with basal insulin and metformin, but increases the frequency of hypolycaemia.     

Adding pharmacists to primary care teams reduces predicted long‐term risk of cardiovascular events in Type 2 diabetic patients without established cardiovascular disease: results from a randomized trial

Aim To determine the impact of adding pharmacists to primary care teams on predicted 10‐year risk of cardiovascular events in patients with Type 2 diabetes without established cardiovascular disease. Methods This was a pre‐specified secondary analysis of randomized trial data. The main study found that, compared with usual care, addition of a pharmacist resulted in improvements in blood pressure, dyslipidaemia, and hyperglycaemia for primary care patients with Type 2 diabetes. In this sub‐study, predicted 10‐year risk of cardiovascular events at baseline and 1 year were calculated for patients free of cardiovascular disease at enrolment. The primary outcome was change in UK Prospective Diabetes Study (UKPDS) risk score; change in Framingham risk score was a secondary outcome. Results Baseline characteristics were similar between the 102 intervention patients and 93 control subjects: 59% women, median (interquartile range) age 57 (50–64) years, diabetes duration 3 (1–6.5) years, systolic blood pressure 128 (120–140) mmHg, total cholesterol 4.34 (3.75–5.04) mmol/l and HbA_1c 54 mmol/mol (48–64 mmol/mol) [7.1% (6.5–8.0%)]. Median baseline UKPDS risk score was 10.2% (6.0–16.7%) for intervention patients and 9.5% (5.8–15.1%) for control subjects (P = 0.80). One‐year post‐randomization, the median absolute reduction in UKPDS risk score was 1.0% greater for intervention patients compared with control subjects (P = 0.032). Similar changes were seen with the Framingham risk score (median reduction 1.2% greater for intervention patients compared with control subjects, P = 0.048). The two risk scores were highly correlated (rho = 0.83; P < 0.001). Conclusion Adding pharmacists to primary care teams for 1 year significantly reduced the predicted 10‐year risk of cardiovascular events for patients with Type 2 diabetes without established cardiovascular disease.     

Effect of nutritional counseling on low-density lipoprotein cholesterol among Thai HIV-infected adults receiving antiretroviral therapy

HIV-infected patients receiving antiretroviral therapy have increased risk of metabolic syndrome, including dyslipidemia. In this study, we determined whether individual nutritional counseling reduced dyslipidemia, particularly low-density lipoprotein (LDL) cholesterol, among HIV-infected patients with dyslipidemia not currently taking lipid-lowering medication. We conducted a randomized 24-week trial among HIV-infected patients with dyslipidemia who were on antiretroviral therapy and were eligible to initiate therapeutic lifestyle changes according to the Thai National Cholesterol Education Program. Participants were randomly assigned to an intervention group that received individual counseling with a nutritionist for seven sessions (baseline, weeks 2, 4, 8, 12, 18, and 24) and a control group that received standard verbal diet information at baseline and nutritional counseling only at week 24. A 24-h recall technique was used to assess dietary intake for both groups at baseline and week 24. Lipid profile (total cholesterol, LDL, high-density lipoprotein (HDL), and triglyceride) was measured at baseline and after 12 and 24 weeks of therapy. An intention-to-treat and linear mixed model were used. Seventy-two patients were randomly assigned, and 62 (86%) participants completed their lipid profile test. After 12 weeks of follow-up, there were significant reductions in the intervention group for total cholesterol (?14.4?±?4.6?mg/dL, P?=?.002), LDL cholesterol (?13.7?±?4.1?mg/dL, P?=?.001), and triglyceride (?30.4?±?13.8?mg/dL, P?=?.03). A significant reduction in LDL cholesterol was also observed in the control group (?7.7?±?3.8?mg/dL, P?=?.04), but there were no significant differences in change of mean lipid levels between the groups at 12 weeks of follow-up. After 24 weeks, participants assigned to the intervention group demonstrated significantly greater decreases in serum total cholesterol (?19.0?±?4.6?vs. 0.2?±?4.3?mg/dL, P?=?.003) and LDL cholesterol (?21.5?±?4.1?vs. ?6.8?±?3.8?mg/dL, P?=?.009). There were no significant changes in HDL cholesterol or triglyceride levels in either group.     

Effect of Combination Therapy of Troglitazone and Sulphonylureas in Patients with Type 2 Diabetes Who Were Poorly Controlled by Sulphonylurea Therapy Alone

The clinical efficacy of troglitazone, a new oral hypoglycaemic agent was investigated in Type 2 diabetes in combination with sulphonylureas. Two hundred and ninety-one patients with Type 2 diabetes (age 21–81 years) whose previous glycaemic control by sulphonylureas was judged stable but unsatisfactory (fasting plasma glucose (FPG) > 8.3 mmol l⁻¹) were randomly allocated into the troglitazone treatment group (troglitazone group, n = 145) or the placebo treatment group (placebo group, n = 146). They were treated by test drugs for 12 weeks in combination with the same dose of sulphonylureas before the trial. One hundred and twenty-two patients who received troglitazone and 126 patients who received placebo were evaluated for efficacy. The baseline characteristics did not differ significantly between the two groups. In the troglitazone group, FPG and HbA_1C decreased significantly after the treatment (before vs after, FPG: 10.8 ± 2.0 mmol l⁻¹ vs 9.2 ± 2.5 mmol l⁻¹, p < 0.001; HbA_1C: 9.2 ± 1.4 % vs 8.5 ± 1.5 %, p < 0.001). FPG and HbA_1C did not change after the treatment in the placebo group (before vs after, FPG: 10.5 ± 1.7 mmol l⁻¹ vs 10.7 ± 2.2 mmol l⁻¹; HbA_1C: 9.0 ± 1.5 % vs 9.2 ± 1.6 %). Serum total cholesterol and HDL-cholesterol did not change in either group, however, serum triglyceride significantly decreased in the troglitazone group. No serious adverse events occurred in either group. In conclusion, troglitazone 400 mg day⁻¹ had a significant hypoglycaemic effect in combination with sulphonylureas without any serious adverse events. Troglitazone, developed as an insulin action enhancer, can be a useful hypoglycaemic agent in the treatment of patients with Type 2 diabetes who are not well controlled by sulphonylureas alone.     

Delay of Type I diabetes in high risk, first degree relatives by parenteral antigen administration: the Schwabing Insulin Prophylaxis Pilot Trial

Summary The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pilot study designed to examine whether insulin therapy can delay or prevent the clinical onset of Type I diabetes in high risk first degree relatives of people with the disease. First degree relatives of patients with Type I diabetes, who were aged 4 years or more, had an islet cell antibody (ICA) value more than 20 Junevile Diabetes Foundation Units (JDF-U), a reduced first phase insulin response (FPI) to an i. v. glucose tolerance test less than the 5th centile, and a normal oral glucose tolerance test were eligible for the trial. Between January 1989 and October 1995, 1736 relatives of patients with Type I diabetes were screened for ICA. We identified 64 cases (3.7 %) with ICA values more than 20 JDF-U. Of ICA positive relatives, 17 (27 %) had a low FPI and were eligible for enrolment. Of these 14 agreed to participate, of whom 7 were randomised to the treatment group and 7 to the control group. In the treatment group, human insulin was administered i. v. by continuous infusion for 7 days, followed by daily s. c. injections for 6 months. Intravenous insulin infusions were repeated every 12 months. In the treatment group 3 of the 7 individuals (follow-up from time of eligibility: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated individuals (1.7 to 7.1 years) developed clinical diabetes. Life table analysis showed that clinical onset of Type I diabetes was delayed in insulin-treated subjects compared with control subjects (means ± SEM diabetes-free survival: 5.0 ± 0.9 years vs 2.3 ± 0.7 years, p < 0.03). Insulin levels after i. v. glucose increased in the first year of intervention therapy. Titres of ICA, and antibodies to glutamic acid decarboxylase, and tyrosine phosphatase-like protein IA2 remained unchanged. These data suggest that insulin prophylaxis can delay the onset of overt diabetes in high risk relatives. This is encouraging in view of 1) the continuing American Diabetes Prevention Trial, which is currently testing the effect of parenteral insulin in a large nation-wide study and 2) the initiation of pilot trials to determine whether new antigen-specific intervention is more effective in delaying the clinical onset of Type I diabetes. [Diabetologia (1998) 41: 536–541] Received: 2 September 1997 and in revised form: 20 December 1997