Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial.

The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14% as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic-euglycaemic-euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14%, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9%. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14% with the FO supplement, the enrichment in muscle membranes remained lower (8%; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT.

Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010.

IMPORTANCE: Type 1 diabetes has historically been associated with a significant reduction in life expectancy. Major advances in treatment of type 1 diabetes have occurred in the past 3 decades. Contemporary estimates of the effect of type 1 diabetes on life expectancy are needed. OBJECTIVE: To examine current life expectancy in people with and without type 1 diabetes in Scotland. We also examined whether any loss of life expectancy in patients with type 1 diabetes is confined to those who develop kidney disease. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort of all individuals alive in Scotland with type 1 diabetes who were aged 20 years or older from 2008 through 2010 and were in a nationwide register (n=24,691 contributing 67,712 person-years and 1043 deaths). MAIN OUTCOMES AND MEASURES: Differences in life expectancy between those with and those without type 1 diabetes and the percentage of the difference due to various causes. RESULTS: Life expectancy at an attained age of 20 years was an additional 46.2 years among men with type 1 diabetes and 57.3 years among men without it, an estimated loss in life expectancy with diabetes of 11.1 years (95% CI, 10.1-12.1). Life expectancy from age 20 years was an additional 48.1 years among women with type 1 diabetes and 61.0 years among women without it, an estimated loss with diabetes of 12.9 years (95% CI, 11.7-14.1). Even among those with type 1 diabetes with an estimated glomerular filtration rate of 90 mL/min/1.73 m2 or higher, life expectancy was reduced (49.0 years in men, 53.1 years in women) giving an estimated loss from age 20 years of 8.3 years (95% CI, 6.5-10.1) for men and 7.9 years (95% CI, 5.5-10.3) for women. Overall, the largest percentage of the estimated loss in life expectancy was related to ischemic heart disease (36% in men, 31% in women) but death from diabetic coma or ketoacidosis was associated with the largest percentage of the estimated loss occurring before age 50 years (29.4% in men, 21.7% in women). CONCLUSIONS AND RELEVANCE: Estimated life expectancy for patients with type 1 diabetes in Scotland based on data from 2008 through 2010 indicated an estimated loss of life expectancy at age 20 years of approximately 11 years for men and 13 years for women compared with the general population without type 1 diabetes.

Platelet-derived microparticle count and surface molecule expression differ between subjects with and without type 2 diabetes, independently of obesity status.

This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study.

BACKGROUND: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM. METHODS AND FINDINGS: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005-2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4-3.8, p<0.001) than men (2.3: 2.0-2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2-3.0, p<0.001) in men and 2.7 (2.2-3.4, p<0.001) in women. Between 2005-2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60-69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA(1c) of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used. CONCLUSIONS: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed. Please see later in the article for the Editors' Summary.

Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

BACKGROUND: Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. METHODS: We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. FINDINGS: Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported. INTERPRETATION: Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. FUNDING: The Wellcome Trust.

Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes.

OBJECTIVE: To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks' gestation, respectively). RESULTS: FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6-21.4] vs. 12.7 ng/mL [interquartile range 9.6-17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6-25.8] vs. 14.6 ng/mL [interquartile range 10.8-19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24-6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. CONCLUSIONS: Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes.

Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes.

OBJECTIVE: To assess the relationship between second and third trimester glycemic control and adverse outcomes in pregnant women with type 1 diabetes, as uncertainty exists about optimum glycemic targets. RESEARCH DESIGN AND METHODS: Pregnancy outcomes were assessed prospectively in 725 women with type 1 diabetes from the Diabetes and Pre-eclampsia Intervention Trial. HbA1c (A1C) values at 26 and 34 weeks' gestation were categorized into five groups, the lowest, <6.0% (42 mmol/mol), being the reference. Average pre- and postprandial results from an eight-point capillary glucose profile the previous day were categorized into five groups, the lowest (preprandial <5.0 mmol/L and postprandial <6.0 mmol/L) being the reference. RESULTS: An A1C of 6.0-6.4% (42-47 mmol/mol) at 26 weeks' gestation was associated with a significantly increased risk of large for gestational age (LGA) (odds ratio 1.7 [95% CI 1.0-3.0]) and an A1C of 6.5-6.9% (48-52 mmol/mol) with a significantly increased risk of preterm delivery (odds ratio 2.5 [95% CI 1.3-4.8]), pre-eclampsia (4.3 [1.7-10.8]), need for a neonatal glucose infusion (2.9 [1.5-5.6]), and a composite adverse outcome (3.2 [1.3-8.0]). These risks increased progressively with increasing A1C. Results were similar at 34 weeks' gestation. Glucose data showed less consistent trends, although the risk of a composite adverse outcome increased with preprandial glucose levels between 6.0 and 6.9 mmol/L at 34 weeks (3.3 [1.3-8.0]). CONCLUSIONS: LGA increased significantly with an A1C ≥6.0 (42 mmol/mol) at 26 and 34 weeks' gestation and with other adverse outcomes with an A1C ≥6.5% (48 mmol/mol). The data suggest that there is clinical utility in regular measurement of A1C during pregnancy.

Cushing's syndrome during pregnancy: curative adrenalectomy at 31 weeks gestation.

A case of Cushing's syndrome due to benign adrenal adenoma (Ad) arising in pregnancy is described. Accurate tumour localisation with magnetic resonance imaging facilitated definitive surgical intervention. Curative adrenalectomy was performed via a posterior approach in the third trimester with subsequent uncomplicated delivery of a healthy infant.

Oat-enriched diet reduces inflammatory status assessed by circulating cell-derived microparticle concentrations in type 2 diabetes.

SCOPE: Inflammatory status can increase the risk of adverse cardiovascular events linked to platelet activity and involvement of microparticles (MP) released from platelets (PMP), leukocytes (LMP), and monocytes (MMP). These MP carry host cell-derived antigens that may act as markers of metabolic health. Subjects newly diagnosed with type 2 diabetes are offered appropriate standard dietary advice (SDA) but this may not be optimal as specific inclusion of other nutrients, such as oats, may add benefit. The effectiveness of such interventions can be tested by examination of MP activation markers. METHODS AND RESULTS: Subjects (n = 22) with type 2 diabetes participated in a randomized cross-over trial involving 8 wk interventions with either an oat-enriched diet (OAT) or following reinforced SDA. Responses were also compared with preintervention habitual (HAB) intake. OAT reduced the concentrations and proportions of fibrinogen- and tissue factor-related PMP and MMP_11b. The main effect of SDA was to reduce fibrinogen-activated PMP. Regardless of chronic intake, a healthy test meal led to postprandial declines in total PMP as well as tissue factor-, fibrinogen-, and P-selectin-positive PMP. CONCLUSION: OAT improved risk factors assessed by MP status, even in subjects with type 2 diabetes already well-controlled by diet and life-style alone.

The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes.

OBJECTIVE: To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial. RESULTS: Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120-423] vs. 365 pg/mL [237-582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108-3,393] vs. 1,193 pg/mL [844-1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9-7.9] vs. 5.1 ng/mL[(4.3-6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17-71] vs. 71 [44-114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4-15.7] vs. 3.1 [1.8-5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001). CONCLUSIONS: These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Optimal glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes in the diabetes and pre-eclampsia intervention trial.

OBJECTIVE: To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA(1c) (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks' gestation (n = 592), and at 34 weeks' gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1-6.9%), moderate (7.0-7.9%), and poor (≥8.0%) glycemic control, respectively. RESULTS: Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C ≥ 8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17-11.6]) compared with optimal control. At 26 weeks' gestation, A1C values ≥ 6.1% (good: 2.09 [1.03-4.21]; moderate: 3.20 [1.47-7.00]; and poor: 3.81 [1.30-11.1]) and at 34 weeks' gestation A1C values ≥ 7.0% (moderate: 3.27 [1.31-8.20] and poor: 8.01 [2.04-31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks' gestation, and at 34 weeks' gestation were 0.88 (0.75-1.03), 0.75 (0.64-0.88), 0.57 (0.42-0.78), and 0.47 (0.31-0.70), respectively. Glycemic control was not significantly associated with gestational hypertension. CONCLUSIONS: Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.

Food intake and dietary glycaemic index in free-living adults with and without type 2 diabetes mellitus.

UNLABELLED: A recent Cochrane review concluded that low glycaemic index (GI) diets are beneficial in glycaemic control for patients with type 2 diabetes mellitus (T2DM). There are limited UK data regarding the dietary GI in free-living adults with and without T2DM. We measured the energy and macronutrient intake and the dietary GI in a group (n = 19) of individuals with diet controlled T2DM and a group (n = 19) without diabetes, matched for age, BMI and gender. Subjects completed a three-day weighed dietary record. Patients with T2DM consumed more daily portions of wholegrains (2.3 vs. 1.1, P = 0.003), more dietary fibre (32.1 vs. 20.9 g, P < 0.001) and had a lower diet GI (53.5 vs. 57.7, P = 0.009) than subjects without T2DM. Both groups had elevated fat and salt intake and low fruit and vegetable intake, relative to current UK recommendations. CONCLUSIONS: Patients with T2DM may already consume a lower GI diet than the general population but further efforts are needed to reduce dietary GI and achieve other nutrient targets.

Outcomes of pregnancies in women with type 1 diabetes in Scotland: a national population-based study.

OBJECTIVE: To determine the outcomes of pregnancies in women with pre-existing, type 1 diabetes. DESIGN: Prospective, population-based cohort. SETTING: Scotland. POPULATION: All 273 women with type 1 diabetes with a pregnancy ending (in miscarriage, abortion or delivery) during the 12 months (from April 1, 1998 to March 31, 1999). METHODS: Pregnancies identified prospectively by clinicians in each hospital; outcome data collected from case records and from Scottish national data sets. MAIN OUTCOME MEASURES: Perinatal and infant mortality, congenital anomaly and birthweight. RESULTS: Of the 273 pregnancies, 40 (14.7%) ended in miscarriage, 20 (7.3%) in abortion and 213 (78%) in delivery. Three deliveries were twin births, thus 216 babies were born. Stillbirth rate (4/216): 18.5 (95% CI 5.1-46.8) per 1000 total births; perinatal mortality rate (6/216): 27.8 (95% CI 10.2-59.4) per 1000 births. There were 13 verified congenital anomalies (in six abortions and seven live births), anomaly rate: 60 (95% CI 32-101) per 1000 total births. Among 208 singleton, live born infants, the mean birthweight was 3427 g. Standardised birthweight scores, relative to a reference population, showed a unimodal distribution, shifted to the right (mean, 1.57 SD). CONCLUSIONS: In an unselected population, adverse outcomes remain more common among the infants of mothers with type 1 diabetes than in the general population. The targets of the St Vincent Declaration of 1989 have not been met. Improvements may be gained by increases in provision of prepregnancy care and in the proportion of pregnancies that are planned. However, further research is needed to clarify the root causes of adverse outcomes in the pregnancies of women with diabetes.